179 results match your criteria Bone research[Journal]


Long noncoding RNAs: a missing link in osteoporosis.

Bone Res 2019 27;7:10. Epub 2019 Mar 27.

1i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.

Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk, particularly in the vertebrae and the hip. This condition and associated morbidity and mortality increase with population ageing. Long noncoding (lnc) RNAs are transcripts longer than 200 nucleotides that are not translated into proteins, but play important regulatory roles in transcriptional and post-transcriptional regulation. Read More

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http://dx.doi.org/10.1038/s41413-019-0048-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437190PMC
March 2019
2 Reads

Pathological mechanisms and therapeutic outlooks for arthrofibrosis.

Bone Res 2019 26;7. Epub 2019 Mar 26.

1School of Biomedical Sciences, University of Western Australia, Crawley, Western Australia Australia.

Arthrofibrosis is a fibrotic joint disorder that begins with an inflammatory reaction to insults such as injury, surgery and infection. Excessive extracellular matrix and adhesions contract pouches, bursae and tendons, cause pain and prevent a normal range of joint motion, with devastating consequences for patient quality of life. Arthrofibrosis affects people of all ages, with published rates varying. Read More

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http://www.nature.com/articles/s41413-019-0047-x
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http://dx.doi.org/10.1038/s41413-019-0047-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433953PMC
March 2019
7 Reads

Enhanced cortical bone expansion in -deficient mice during aging.

Bone Res 2018 26;6. Epub 2018 Mar 26.

Center for Cancer and Cell Biology, Program for Skeletal Disease and Tumor Microenvironment, Van Andel Research Institute, Grand Rapids, MI USA.

Imbalances between bone formation and bone resorption, which can occur due to aging or sex hormone deprivation, result in decreased bone mass and an increased risk of fracture. Previous studies have suggested that the β-galactoside binding lectin, galectin-3, is involved in bone remodeling. We compared bone parameters of mice having null alleles of the galectin-3 gene (-KO) with those of their wild-type littermates. Read More

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http://dx.doi.org/10.1038/s41413-017-0003-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416267PMC

Collagen type II suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin β1-SMAD1 interaction.

Bone Res 2019 6;7. Epub 2019 Mar 6.

1Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China.

Hypertrophic differentiation is not only the terminal process of endochondral ossification in the growth plate but is also an important pathological change in osteoarthritic cartilage. Collagen type II (COL2A1) was previously considered to be only a structural component of the cartilage matrix, but recently, it has been revealed to be an extracellular signaling molecule that can significantly suppress chondrocyte hypertrophy. However, the mechanisms by which COL2A1 regulates hypertrophic differentiation remain unclear. Read More

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http://dx.doi.org/10.1038/s41413-019-0046-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403405PMC
March 2019
1 Read

Characterization of a novel murine Sost ER Cre model targeting osteocytes.

Bone Res 2019 21;7. Epub 2019 Feb 21.

1Department of Oral and Craniofacial Sciences, University of Missouri-Kansas City School of Dentistry, Kansas City, MO USA.

Transgenic mice are widely used to delete or overexpress genes in a cell specific manner to advance knowledge of bone biology, function and disease. While numerous Cre models exist to target gene recombination in osteoblasts and osteoclasts, few target osteocytes specifically, particularly mature osteocytes. Our goal was to create a spatial and temporal conditional Cre model using tamoxifen to induce Cre activity in mature osteocytes using a Bac construct containing the 5' and 3' regions of the gene (Sost ER Cre). Read More

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http://dx.doi.org/10.1038/s41413-018-0037-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382861PMC
February 2019
1 Read

Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual.

Bone Res 2019 21;7. Epub 2019 Feb 21.

1Department of Orthopaedic Surgery, School of Medicine, University of Michigan, Ann Arbor, MI USA.

Osteoblasts, which are the bone-forming cells, operate in a hypoxic environment. The transcription factors hypoxia-inducible factor-1α (HIF1) and HIF2 are key mediators of the cellular response to hypoxia. Both are expressed in osteoblasts. Read More

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http://dx.doi.org/10.1038/s41413-019-0045-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382776PMC
February 2019
3 Reads

Activation of mTORC1 in subchondral bone preosteoblasts promotes osteoarthritis by stimulating bone sclerosis and secretion of CXCL12.

Bone Res 2019 20;7. Epub 2019 Feb 20.

1Department of Orthopedics, Academy of Orthopedics-Guangdong Province, The Third Affiliated Hospital of Southern Medical University, 510630 Guangzhou, China.

Increasing evidences show that aberrant subchondral bone remodeling plays an important role in the development of osteoarthritis (OA). However, how subchondral bone formation is activated and the mechanism by which increased subchondral bone turnover promotes cartilage degeneration during OA remains unclear. Here, we show that the mechanistic target of rapamycin complex 1 (mTORC1) pathway is activated in subchondral bone preosteoblasts (Osterix+) from OA patients and mice. Read More

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http://dx.doi.org/10.1038/s41413-018-0041-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381187PMC
February 2019
1 Read

The potential risks of C-C chemokine receptor 5-edited babies in bone development.

Bone Res 2019 29;7. Epub 2019 Jan 29.

1Department of Orthopedics, Chinese PLA General Hospital, Beijing, China.

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http://dx.doi.org/10.1038/s41413-019-0044-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351561PMC
January 2019

Erratum: Author Correction: Exosomes-the enigmatic regulators of bone homeostasis.

Bone Res 2019 25;7. Epub 2019 Jan 25.

1Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA 6009 Australia.

[This corrects the article DOI: 10.1038/s41413-018-0039-2.]. Read More

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http://dx.doi.org/10.1038/s41413-018-0043-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347613PMC
January 2019
2 Reads

NOTUM inhibition increases endocortical bone formation and bone strength.

Bone Res 2019 8;7. Epub 2019 Jan 8.

1Lexicon Pharmaceuticals, The Woodlands, TX USA.

The disability, mortality and costs caused by non-vertebral osteoporotic fractures are enormous. Existing osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral fractures. Cortical bone is a major determinant of non-vertebral bone strength. Read More

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http://www.nature.com/articles/s41413-018-0038-3
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http://dx.doi.org/10.1038/s41413-018-0038-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323125PMC
January 2019
9 Reads

Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis.

Bone Res 2019 3;7. Epub 2019 Jan 3.

1Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo Japan.

Bone is one of the preferred sites for the metastasis of malignant tumours, such as breast cancer, lung cancer and malignant melanoma. Tumour cells colonizing bone have the capacity to induce the expression of receptor activator of nuclear factor-κB ligand (RANKL), which promotes osteoclast differentiation and activation. Tumour-induced osteoclastic bone resorption leads to a vicious cycle between tumours and bone cells that fuels osteolytic tumour growth, causing bone pain and hypercalcaemia. Read More

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http://dx.doi.org/10.1038/s41413-018-0036-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315020PMC
January 2019
2 Reads

Nucleic acids and analogs for bone regeneration.

Bone Res 2018 27;6:37. Epub 2018 Dec 27.

1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 People's Republic of China.

With the incidence of different bone diseases increasing, effective therapies are needed that coordinate a combination of various technologies and biological materials. Bone tissue engineering has also been considered as a promising strategy to repair various bone defects. Therefore, different biological materials that can promote stem cell proliferation, migration, and osteoblastic differentiation to accelerate bone tissue regeneration and repair have also become the focus of research in multiple fields. Read More

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http://www.nature.com/articles/s41413-018-0042-7
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http://dx.doi.org/10.1038/s41413-018-0042-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306486PMC
December 2018
7 Reads

Exosomes-the enigmatic regulators of bone homeostasis.

Bone Res 2018 7;6:36. Epub 2018 Dec 7.

1Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA 6009 Australia.

Exosomes are a heterogeneous group of cell-derived membranous structures, which mediate crosstalk interaction between cells. Recent studies have revealed a close relationship between exosomes and bone homeostasis. It is suggested that bone cells can spontaneously secret exosomes containing proteins, lipids and nucleic acids, which then to regulate osteoclastogenesis and osteogenesis. Read More

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http://dx.doi.org/10.1038/s41413-018-0039-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286319PMC
December 2018
2 Reads

RANKL-RANK signaling regulates osteoblast differentiation and bone formation.

Authors:
Xu Cao

Bone Res 2018 27;6:35. Epub 2018 Nov 27.

Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Ross Building, Room 229, 720 Rutland Ave, Baltimore, MD 21205 USA.

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http://dx.doi.org/10.1038/s41413-018-0040-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255775PMC
November 2018

RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation.

Bone Res 2018 27;6:34. Epub 2018 Nov 27.

1Department of Orthopedics Trauma, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.

RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone marrow mesenchymal stem cells (BMSCs) during osteogenic differentiation in both mice and human and decreased rapidly. Read More

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http://dx.doi.org/10.1038/s41413-018-0035-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255918PMC
November 2018

Gα signaling controls intramembranous ossification during cranial bone development by regulating both Hedgehog and Wnt/β-catenin signaling.

Bone Res 2018 20;6:33. Epub 2018 Nov 20.

1Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA USA.

How osteoblast cells are induced is a central question for understanding skeletal formation. Abnormal osteoblast differentiation leads to a broad range of devastating craniofacial diseases. Here we have investigated intramembranous ossification during cranial bone development in mouse models of skeletal genetic diseases that exhibit craniofacial bone defects. Read More

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http://www.nature.com/articles/s41413-018-0034-7
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http://dx.doi.org/10.1038/s41413-018-0034-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242855PMC
November 2018
9 Reads

NUMB maintains bone mass by promoting degradation of PTEN and GLI1 via ubiquitination in osteoblasts.

Bone Res 2018 10;6:32. Epub 2018 Nov 10.

2The Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York City, NY 10029 USA.

The adaptor protein NUMB is involved in asymmetric division and cell fate determination and recognized as an antagonist of Notch. Previous studies have proved that Notch activation in osteoblasts contributes to a high bone mass. In this study,  however, an osteopenic phenotype was found in 9-week-old mice using osteoblastic specific  to ablate both and its homologue . Read More

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http://dx.doi.org/10.1038/s41413-018-0030-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226489PMC
November 2018
22 Reads

Advanced smart biomaterials and constructs for hard tissue engineering and regeneration.

Bone Res 2018 22;6:31. Epub 2018 Oct 22.

2Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD USA.

Hard tissue repair and regeneration cost hundreds of billions of dollars annually worldwide, and the need has substantially increased as the population has aged. Hard tissues include bone and tooth structures that contain calcium phosphate minerals. Smart biomaterial-based tissue engineering and regenerative medicine methods have the exciting potential to meet this urgent need. Read More

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http://www.nature.com/articles/s41413-018-0032-9
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http://dx.doi.org/10.1038/s41413-018-0032-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196224PMC
October 2018
24 Reads

BMP-IHH-mediated interplay between mesenchymal stem cells and osteoclasts supports calvarial bone homeostasis and repair.

Bone Res 2018 17;6:30. Epub 2018 Oct 17.

1Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA USA.

Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells (MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and repair. Abnormal function of osteogenic cells or diminished MSCs within the cranial suture can lead to skull defects, such as craniosynostosis. Read More

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http://dx.doi.org/10.1038/s41413-018-0031-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193039PMC
October 2018

Commentary on "Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via endogenous apoptosis".

Authors:
J Edward Puzas

Bone Res 2018 17;6:29. Epub 2018 Oct 17.

University of Rochester School of Medicine and Dentistry, Rochester, NY USA.

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http://www.nature.com/articles/s41413-018-0033-8
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http://dx.doi.org/10.1038/s41413-018-0033-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191457PMC
October 2018
12 Reads

Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via endogenous apoptosis.

Bone Res 2018 11;6:28. Epub 2018 Sep 11.

1Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China.

Signal transduction between different organs is crucial in the normal development of the human body. As an important medium for signal communication, exosomes can transfer important information, such as microRNAs (miRNAs), from donors to receptors. MiRNAs are known to fine-tune a variety of biological processes, including maxillofacial development; however, the underlying mechanism remains largely unknown. Read More

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http://dx.doi.org/10.1038/s41413-018-0028-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131536PMC
September 2018
5 Reads

prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells.

Bone Res 2018 11;6:27. Epub 2018 Sep 11.

1MS-State Key Laboratory & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, China.

Mutations in the liver/bone/kidney alkaline phosphatase () gene cause hypophosphatasia (HPP) and early-onset bone dysplasia, suggesting that this gene is a key factor in human bone development. However, how and where acts in bone ageing is largely unknown. Here, we determined that ablation of induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16 (p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells (MSCs). Read More

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http://www.nature.com/articles/s41413-018-0029-4
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http://dx.doi.org/10.1038/s41413-018-0029-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131243PMC
September 2018
5 Reads

Aberrant activation of latent transforming growth factor-β initiates the onset of temporomandibular joint osteoarthritis.

Bone Res 2018 11;6:26. Epub 2018 Sep 11.

1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

There is currently no effective medical treatment for temporomandibular joint osteoarthritis (TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transforming growth factor-β (TGF-β) signalling in the cartilage and subchondral bone of the TMJ using a temporomandibular joint disorder (TMD) rat model, an ageing mouse model and a Camurati-Engelmann disease (CED) mouse model. In the three animal models, the subchondral bone phenotypes in the mandibular condyles were evaluated by µCT, and changes in TMJ condyles were examined by TRAP staining and immunohistochemical analysis of Osterix and p-Smad2/3. Read More

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http://www.nature.com/articles/s41413-018-0027-6
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http://dx.doi.org/10.1038/s41413-018-0027-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131160PMC
September 2018
13 Reads

Biomimetic delivery of signals for bone tissue engineering.

Bone Res 2018 29;6:25. Epub 2018 Aug 29.

1Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI USA.

Bone tissue engineering is an exciting approach to directly repair bone defects or engineer bone tissue for transplantation. Biomaterials play a pivotal role in providing a template and extracellular environment to support regenerative cells and promote tissue regeneration. A variety of signaling cues have been identified to regulate cellular activity, tissue development, and the healing process. Read More

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http://dx.doi.org/10.1038/s41413-018-0025-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115422PMC
August 2018
4 Reads

R-spondin-2 is a Wnt agonist that regulates osteoblast activity and bone mass.

Bone Res 2018 14;6:24. Epub 2018 Aug 14.

1Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.

The R-spondin family of proteins are Wnt agonists, and the complete embryonic disruption of results in skeletal developmental defects that recapitulate the phenotype observed with deficiency. Previous work has shown that R-spondin-2 (, RSPO2) is both highly expressed in Wnt-stimulated pre-osteoblasts and its overexpression induces osteoblast differentiation in the same cells, supporting its putative role as a positive autocrine regulator of osteoblastogenesis. However, the role of Rspo2 in regulating osteoblastogenesis and bone formation in postnatal bone has not been explored. Read More

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http://dx.doi.org/10.1038/s41413-018-0026-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089978PMC
August 2018
16 Reads

A peptide containing the receptor binding site of insulin-like growth factor binding protein-2 enhances bone mass in ovariectomized rats.

Bone Res 2018 14;6:23. Epub 2018 Aug 14.

1Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, USA.

Male -- mice have a significant reduction in bone mass and administration of a peptide that contains the insulin-like growth factor binding protein-2(IGFBP-2) receptor-binding domain stimulates bone formation in these animals. Female -/- mice do not have this phenotype but following ovariectomy (OVX) lose more bone than OVX wild-type mice. This suggests that in the absence of estrogen, IGFBP-2 is required to maintain bone mass. Read More

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http://dx.doi.org/10.1038/s41413-018-0024-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089876PMC
August 2018
1 Read

Oxidized phospholipids are ligands for LRP6.

Bone Res 2018 18;6:22. Epub 2018 Jul 18.

2Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, 21205 MD USA.

Low-density lipoprotein receptor-related protein 6 (LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation. The ligands that bind directly to LRP6 have not been identified. Here, we report that bioactive oxidized phospholipids (oxPLs) are native ligands of LRP6, but not the closely related LRP5. Read More

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http://dx.doi.org/10.1038/s41413-018-0023-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050227PMC
July 2018
12 Reads

Ciliary parathyroid hormone signaling activates transforming growth factor-β to maintain intervertebral disc homeostasis during aging.

Bone Res 2018 18;6:21. Epub 2018 Jul 18.

1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Ross Building, Room 229, 720 Rutland Ave, Baltimore, MD USA.

Degenerative disc disease (DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor (PTH1R) to the cilia and enhances parathyroid hormone (PTH) signaling in NP cells. Read More

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http://dx.doi.org/10.1038/s41413-018-0022-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050246PMC
July 2018
6 Reads

Dietary fat-associated osteoarthritic chondrocytes gain resistance to lipotoxicity through PKCK2/STAMP2/FSP27.

Bone Res 2018 6;6:20. Epub 2018 Jul 6.

2Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, Republic of Korea.

Free fatty acids (FFAs), which are elevated with metabolic syndrome, are considered the principal offender exerting lipotoxicity. Few previous studies have reported a causal relationship between FFAs and osteoarthritis pathogenesis. However, the molecular mechanism by which FFAs exert lipotoxicity and induce osteoarthritis remains largely unknown. Read More

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http://dx.doi.org/10.1038/s41413-018-0020-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033867PMC
July 2018
11 Reads

The art of building bone: emerging role of chondrocyte-to-osteoblast transdifferentiation in endochondral ossification.

Bone Res 2018 14;6:19. Epub 2018 Jun 14.

Musculoskeletal Disease Center, Veterans Affairs Loma Linda Healthcare System, Loma Linda, California USA.

There is a worldwide epidemic of skeletal diseases causing not only a public health issue but also accounting for a sizable portion of healthcare expenditures. The vertebrate skeleton is known to be formed by mesenchymal cells condensing into tissue elements (patterning phase) followed by their differentiation into cartilage (chondrocytes) or bone (osteoblasts) cells within the condensations. During the growth and remodeling phase, bone is formed directly via intramembranous ossification or through a cartilage to bone conversion via endochondral ossification routes. Read More

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http://www.nature.com/articles/s41413-018-0021-z
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http://dx.doi.org/10.1038/s41413-018-0021-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002476PMC
June 2018
2 Reads

YAP promotes osteogenesis and suppresses adipogenic differentiation by regulating β-catenin signaling.

Bone Res 2018 1;6:18. Epub 2018 Jun 1.

1Department of Neuroscience, Case Western Reserve University, Cleveland, OH 44106 USA.

YAP (yes-associated protein) is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone homeostasis remains controversial. Here we provide evidence for YAP's function in promoting osteogenesis, suppressing adipogenesis, and thus maintaining bone homeostasis. Read More

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http://www.nature.com/articles/s41413-018-0018-7
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http://dx.doi.org/10.1038/s41413-018-0018-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984632PMC
June 2018
16 Reads

Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy.

Bone Res 2018 25;6:17. Epub 2018 May 25.

1Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, 169857 Singapore.

Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Read More

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http://dx.doi.org/10.1038/s41413-018-0017-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968037PMC
May 2018
2 Reads

Paracrine and endocrine actions of bone-the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts.

Bone Res 2018 24;6:16. Epub 2018 May 24.

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Sciences, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031 China.

The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes, and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Read More

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http://dx.doi.org/10.1038/s41413-018-0019-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967329PMC
May 2018
5 Reads

Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies.

Bone Res 2018 27;6:15. Epub 2018 Apr 27.

2School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia 6009 Australia.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages: (i) triggering, (ii) maturation, (iii) targeting, and (iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Read More

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http://dx.doi.org/10.1038/s41413-018-0016-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920070PMC
April 2018
3 Reads
1 Citation

Histone demethylase LSD1 regulates bone mass by controlling WNT7B and BMP2 signaling in osteoblasts.

Bone Res 2018 26;6:14. Epub 2018 Apr 26.

1State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031 China.

Multiple regulatory mechanisms control osteoblast differentiation and function to ensure unperturbed skeletal formation and remodeling. In this study we identify histone lysine-specific demethylase 1(LSD1/KDM1A) as a key epigenetic regulator of osteoblast differentiation. Knockdown of LSD1 promoted osteoblast differentiation of human mesenchymal stem cells (hMSCs) in vitro and mice lacking LSD1 in mesenchymal cells displayed increased bone mass secondary to accelerated osteoblast differentiation. Read More

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http://dx.doi.org/10.1038/s41413-018-0015-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916912PMC
April 2018
1 Read

Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone.

Bone Res 2018 25;6:13. Epub 2018 Apr 25.

1Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Gaithersburg, MD USA.

Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody (mAb) probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid (LTA). Specificity and affinity were assessed in vitro. Read More

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http://dx.doi.org/10.1038/s41413-018-0014-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916877PMC
April 2018
7 Reads

SHP2 regulates skeletal cell fate by modifying SOX9 expression and transcriptional activity.

Bone Res 2018 6;6:12. Epub 2018 Apr 6.

1Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, RI 02903 USA.

Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor (OCP), and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2 (encoded by ) affects skeletal lineage commitment by conditionally deleting in mouse limb and head mesenchyme using "Cre-loxP"-mediated gene excision. Read More

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http://dx.doi.org/10.1038/s41413-018-0013-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886981PMC
April 2018
4 Reads

Super enhancer inhibitors suppress MYC driven transcriptional amplification and tumor progression in osteosarcoma.

Bone Res 2018 4;6:11. Epub 2018 Apr 4.

4Institute for Advanced Study, Shenzhen University, Shenzhen, 518060 Guangdong China.

Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. Read More

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http://dx.doi.org/10.1038/s41413-018-0009-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884797PMC
April 2018
9 Reads

CHIP regulates bone mass by targeting multiple TRAF family members in bone marrow stromal cells.

Bone Res 2018 29;6:10. Epub 2018 Mar 29.

2Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612 USA.

Carboxyl terminus of Hsp70-interacting protein (CHIP or STUB1) is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. Read More

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http://dx.doi.org/10.1038/s41413-018-0010-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874245PMC
March 2018
1 Read

Omentin-1 prevents inflammation-induced osteoporosis by downregulating the pro-inflammatory cytokines.

Bone Res 2018 30;6. Epub 2018 Mar 30.

3Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008 China.

Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global knockout () mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Read More

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http://dx.doi.org/10.1038/s41413-018-0012-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876344PMC
March 2018
15 Reads

Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation.

Bone Res 2018 28;6. Epub 2018 Mar 28.

1Department of Cancer Biology and Genetics and Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA.

Genome-wide association studies (GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast- and osteoclast (OC)-specific functions. Read More

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http://dx.doi.org/10.1038/s41413-018-0011-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874256PMC
March 2018
52 Reads

Mechanically induced Ca oscillations in osteocytes release extracellular vesicles and enhance bone formation.

Bone Res 2018 19;6. Epub 2018 Mar 19.

1Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY USA.

The vast osteocytic network is believed to orchestrate bone metabolic activity in response to mechanical stimuli through production of sclerostin, RANKL, and osteoprotegerin (OPG). However, the mechanisms of osteocyte mechanotransduction remain poorly understood. We've previously shown that osteocyte mechanosensitivity is encoded through unique intracellular calcium (Ca) dynamics. Read More

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http://dx.doi.org/10.1038/s41413-018-0007-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859015PMC
March 2018
6 Reads

IGF-I induced phosphorylation of PTH receptor enhances osteoblast to osteocyte transition.

Bone Res 2018 26;6. Epub 2018 Feb 26.

1Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD USA.

Parathyroid hormone (PTH) regulates bone remodeling by activating PTH type 1 receptor (PTH1R) in osteoblasts/osteocytes. Insulin-like growth factor type 1 (IGF-1) stimulates mesenchymal stem cell differentiation to osteoblasts. However, little is known about the signaling mechanisms that regulates the osteoblast-to-osteocyte transition. Read More

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http://dx.doi.org/10.1038/s41413-017-0002-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827661PMC
February 2018
5 Reads

Lrp1 in osteoblasts controls osteoclast activity and protects against osteoporosis by limiting PDGF-RANKL signaling.

Bone Res 2018 26;6. Epub 2018 Feb 26.

1Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1 (Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass. Read More

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http://dx.doi.org/10.1038/s41413-017-0006-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826921PMC
February 2018
2 Reads

Engineering 3D approaches to model the dynamic microenvironments of cancer bone metastasis.

Bone Res 2018 26;6. Epub 2018 Feb 26.

Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011 China.

Cancer metastasis to bone is a three-dimensional (3D), multistep, dynamic process that requires the sequential involvement of three microenvironments, namely, the primary tumour microenvironment, the circulation microenvironment and the bone microenvironment. Engineered 3D approaches allow for a vivid recapitulation of in vivo cancerous microenvironments in vitro, in which the biological behaviours of cancer cells can be assessed under different metastatic conditions. Therefore, modelling bone metastasis microenvironments with 3D cultures is imperative for advancing cancer research and anti-cancer treatment strategies. Read More

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http://www.nature.com/articles/s41413-018-0008-9
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http://dx.doi.org/10.1038/s41413-018-0008-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826951PMC
February 2018
12 Reads

Transforming growth factor-β in stem cells and tissue homeostasis.

Bone Res 2018 31;6. Epub 2018 Jan 31.

4Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD USA.

TGF-β 1-3 are unique multi-functional growth factors that are only expressed in mammals, and mainly secreted and stored as a latent complex in the extracellular matrix (ECM). The biological functions of TGF-β in adults can only be delivered after ligand activation, mostly in response to environmental perturbations. Although involved in multiple biological and pathological processes of the human body, the exact roles of TGF-β in maintaining stem cells and tissue homeostasis have not been well-documented until recent advances, which delineate their functions in a given context. Read More

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http://dx.doi.org/10.1038/s41413-017-0005-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802812PMC
January 2018
4 Reads

mTOR signaling in skeletal development and disease.

Bone Res 2018 30;6. Epub 2018 Jan 30.

3Departments of Orthopaedic Surgery, Medicine and Developmental Biology, Washington University School of Medicine, St. Louis, MO 63131 USA.

The mammalian/mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that integrates inputs from nutrients and growth factors to control many fundamental cellular processes through two distinct protein complexes mTORC1 and mTORC2. Recent mouse genetic studies have established that mTOR pathways play important roles in regulating multiple aspects of skeletal development and homeostasis. In addition, mTORC1 has emerged as a common effector mediating the bone anabolic effect of Igf1, Wnt and Bmp. Read More

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http://dx.doi.org/10.1038/s41413-017-0004-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802487PMC
January 2018
1 Read

Calcium phosphate cements for bone engineering and their biological properties.

Bone Res 2017 20;5:17056. Epub 2017 Dec 20.

Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.

Calcium phosphate cements (CPCs) are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. Read More

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http://dx.doi.org/10.1038/boneres.2017.56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764120PMC
December 2017
5 Reads

Bone biomaterials and interactions with stem cells.

Bone Res 2017 21;5:17059. Epub 2017 Dec 21.

State Key Laboratory of High Performance Complex Manufacturing, College of Mechanical and Electrical Engineering, Central South University, Changsha, China.

Bone biomaterials play a vital role in bone repair by providing the necessary substrate for cell adhesion, proliferation, and differentiation and by modulating cell activity and function. In past decades, extensive efforts have been devoted to developing bone biomaterials with a focus on the following issues: (1) developing ideal biomaterials with a combination of suitable biological and mechanical properties; (2) constructing a cell microenvironment with pores ranging in size from nanoscale to submicro- and microscale; and (3) inducing the oriented differentiation of stem cells for artificial-to-biological transformation. Here we present a comprehensive review of the state of the art of bone biomaterials and their interactions with stem cells. Read More

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http://dx.doi.org/10.1038/boneres.2017.59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738879PMC
December 2017

Multifunctional stimuli responsive polymer-gated iron and gold-embedded silica nano golf balls: Nanoshuttles for targeted on-demand theranostics.

Bone Res 2017 20;5:17051. Epub 2017 Dec 20.

Department of Mechanical and Aerospace Engineering, La Jolla, CA, USA.

Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis, efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles (NP)-embedded silica nanoshuttles (MGNSs) with nanopores on their surface. Read More

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http://dx.doi.org/10.1038/boneres.2017.51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737138PMC
December 2017
61 Reads