137 results match your criteria osteoblast-specific knockout

Osteoblast-Specific Wnt Secretion is Required for Skeletal Homeostasis and Loading-Induced Bone Formation in Adult Mice.

J Bone Miner Res 2021 Sep 20. Epub 2021 Sep 20.

Department of Orthopaedic Surgery and Musculoskeletal Research Center, Washington University School of Medicine, Saint Louis, Missouri, US.

Wnt signaling is critical to many aspects of skeletal regulation, but the importance of Wnt ligands in the bone anabolic response to mechanical loading is not well established. Recent transcriptome profiling studies by our lab and others show that mechanical loading potently induces genes encoding Wnt ligands, including Wnt1 and Wnt7b. Based on these findings, we hypothesized that mechanical loading stimulates adult bone formation by inducing Wnt ligand expression. Read More

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September 2021

The mTORC2 Regulator Homer1 Modulates Protein Levels and Sub-Cellular Localization of the CaSR in Osteoblast-Lineage Cells.

Int J Mol Sci 2021 Jun 17;22(12). Epub 2021 Jun 17.

Discipline of Physiology, School of Medical Sciences and Bosch Institute, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia.

We recently found that, in human osteoblasts, Homer1 complexes to Calcium-sensing receptor (CaSR) and mediates AKT initiation via mechanistic target of rapamycin complex (mTOR) complex 2 (mTORC2) leading to beneficial effects in osteoblasts including β-catenin stabilization and mTOR complex 1 (mTORC1) activation. Herein we further investigated the relationship between Homer1 and CaSR and demonstrate a link between the protein levels of CaSR and Homer1 in human osteoblasts in primary culture. Thus, when siRNA was used to suppress the CaSR, we observed upregulated Homer1 levels, and when siRNA was used to suppress Homer1 we observed downregulated CaSR protein levels using immunofluorescence staining of cultured osteoblasts as well as Western blot analyses of cell protein extracts. Read More

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Low bone mass resulting from impaired estrogen signaling in bone increases severity of load-induced osteoarthritis in female mice.

Bone 2021 11 24;152:116071. Epub 2021 Jun 24.

Cornell University, Ithaca, NY, United States of America; Hospital for Special Surgery, New York, NY, United States of America. Electronic address:

Objective: Reduced subchondral bone mass and increased remodeling are associated with early stage OA. However, the direct effect of low subchondral bone mass on the risk and severity of OA development is unclear. We sought to determine the role of low bone mass resulting from a bone-specific loss of estrogen signaling in load-induced OA development using female osteoblast-specific estrogen receptor-alpha knockout (pOC-ERαKO) mice. Read More

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November 2021

Estrogen receptor α in mature osteoblasts regulates the late stage of bone regeneration.

Biochem Biophys Res Commun 2021 06 5;559:238-244. Epub 2021 May 5.

Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Ehime, Japan; Department of Pathophysiology, Ehime University Graduate School of Medicine, Ehime, Japan. Electronic address:

Estrogen deficiency impairs fracture healing and homeostasis of bone tissue. OVX-induced estrogen deficiency in mice attenuates fracture healing and changes the expression ratio of estrogen receptor (ER) α and ERβ in callus during the process of fracture healing. Therefore, ERs may be involved in the regulation of fracture healing. Read More

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Hypoxia-inducible factor-2α mediates senescence-associated intrinsic mechanisms of age-related bone loss.

Exp Mol Med 2021 Apr 2;53(4):591-604. Epub 2021 Apr 2.

Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea.

Aging is associated with cellular senescence followed by bone loss leading to bone fragility in humans. However, the regulators associated with cellular senescence in aged bones need to be identified. Hypoxia-inducible factor (HIF)-2α regulates bone remodeling via the differentiation of osteoblasts and osteoclasts. Read More

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BMP2-dependent gene regulatory network analysis reveals Klf4 as a novel transcription factor of osteoblast differentiation.

Cell Death Dis 2021 02 19;12(2):197. Epub 2021 Feb 19.

State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Transcription factors (TFs) regulate the expression of target genes, inducing changes in cell morphology or activities needed for cell fate determination and differentiation. The BMP signaling pathway is widely regarded as one of the most important pathways in vertebrate skeletal biology, of which BMP2 is a potent inducer, governing the osteoblast differentiation of bone marrow stromal cells (BMSCs). However, the mechanism by which BMP2 initiates its downstream transcription factor cascade and determines the direction of differentiation remains largely unknown. Read More

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February 2021

Runx1 is a central regulator of osteogenesis for bone homeostasis by orchestrating BMP and WNT signaling pathways.

PLoS Genet 2021 01 21;17(1):e1009233. Epub 2021 Jan 21.

Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States of America.

Runx1 is highly expressed in osteoblasts, however, its function in osteogenesis is unclear. We generated mesenchymal progenitor-specific (Runx1f/fTwist2-Cre) and osteoblast-specific (Runx1f/fCol1α1-Cre) conditional knockout (Runx1 CKO) mice. The mutant CKO mice with normal skeletal development displayed a severe osteoporosis phenotype at postnatal and adult stages. Read More

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January 2021

Osteoblast-specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase-1 engenders insulin resistance in high-fat diet fed mice.

J Cell Physiol 2021 06 10;236(6):4614-4624. Epub 2020 Dec 10.

Functional Genetics and Development, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Midlothian, UK.

Supraphysiological levels of the osteoblast-enriched mineralization regulator ectonucleotide pyrophosphatase or phosphodiesterase-1 (NPP1) is associated with type 2 diabetes mellitus. We determined the impact of osteoblast-specific Enpp1 ablation on skeletal structure and metabolic phenotype in mice. Female, but not male, 6-week-old mice lacking osteoblast NPP1 expression (osteoblast-specific knockout [KO]) exhibited increased femoral bone volume or total volume (17. Read More

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SHP2 regulates the development of intestinal epithelium by modifying OSTERIX crypt stem cell self-renewal and proliferation.

FASEB J 2021 01 9;35(1):e21106. Epub 2020 Nov 9.

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

The protein tyrosine phosphatase SHP2, encoded by PTPN11, is ubiquitously expressed and essential for the development and/or maintenance of multiple tissues and organs. SHP2 is involved in gastrointestinal (GI) epithelium development and homeostasis, but the underlying mechanisms remain elusive. While studying SHP2's role in skeletal development, we made osteoblast-specific SHP2 deficient mice using Osterix (Osx)-Cre as a driver to excise Ptpn11 floxed alleles. Read More

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January 2021

[Generation and validation of inducible osteoblast-specific Stat3 knockout mice].

Shanghai Kou Qiang Yi Xue 2020 Aug;29(4):337-342

Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology. Shanghai 200011, China.

Purpose: Based on the Cre-Loxp gene knockout system, this study intended to construct tamoxifen-inducible STAT3 conditional knockout mice and verify the knockout efficiency.

Methods: The inducible osteoblasts-specific Stat3 knockout mice Stat3Col1ERT2 were obtained by hybridization through C57 mice of Stat3fl/fl and Col1 creERT2. Bone mesenchymal stem cells(BMSCs) of these mice were isolated and cultured with or without 4-hydroxytamoxin(4-OTH), to verify the effect of Stat3 knockout in vitro by real-time quantitative PCR and Western blotting in the level of mRNA and protein. Read More

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Discoidin Domain Receptor 1 Regulates Runx2 during Osteogenesis of Osteoblasts and Promotes Bone Ossification via Phosphorylation of p38.

Int J Mol Sci 2020 Sep 29;21(19). Epub 2020 Sep 29.

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Discoidin domain receptor 1 () is a collagen-binding membrane protein, but its role in osteoblasts during osteogenesis remains undefined. We generated inducible osteoblast-specific knockout (OKOΔ) mice; their stature at birth, body weight and body length were significantly decreased compared with those of control mice. We hypothesize that regulates osteogenesis of osteoblasts. Read More

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September 2020

Inhibition of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) stimulates osteoblastogenesis by potentiating bone morphogenetic protein 2 (BMP2) responses.

J Cell Physiol 2021 02 19;236(2):1195-1213. Epub 2020 Jul 19.

Research Centre, Shriners Hospital for Children - Canada, Montreal, Quebec, Canada.

The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is a pleiotropic enzyme involved in DNA repair, cell cycle control, and transcription regulation. A potential role for DNA-PKcs in the regulation of osteoblastogenesis remains to be established. We show that pharmacological inhibition of DNA-PKcs kinase activity or gene silencing of Prkdc (encoding DNA-PKcs) in murine osteoblastic MC3T3-E1 cells and human adipose-derived mesenchymal stromal cells markedly enhanced osteogenesis and the expression of osteoblast differentiation marker genes. Read More

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February 2021

PPARδ-mediated mitochondrial rewiring of osteoblasts determines bone mass.

Sci Rep 2020 05 21;10(1):8428. Epub 2020 May 21.

Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University Erlangen-Nurnberg and Universitätsklinikum Erlangen, Erlangen, Germany.

Bone turnover, which is determined by osteoclast-mediated bone resorption and osteoblast-mediated bone formation, represents a highly energy consuming process. The metabolic requirements of osteoblast differentiation and mineralization, both essential for regular bone formation, however, remain incompletely understood. Here we identify the nuclear receptor peroxisome proliferator-activated receptor (PPAR) δ as key regulator of osteoblast metabolism. Read More

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Expression of the type 1 lysophosphatidic acid receptor in osteoblastic cell lineage controls both bone mineralization and osteocyte specification.

Biochim Biophys Acta Mol Cell Biol Lipids 2020 08 21;1865(8):158715. Epub 2020 Apr 21.

Pathophysiology, Diagnosis and treatments of bone diseases, INSERM UMR1033, Lyon, France. Electronic address:

Lysphosphatidic acid (LPA) is a major natural bioactive lipid mediator whose biological functions affect multiple organs. These include bone as demonstrated by global Lpar1-knockout mice (Lpar1) which present a bone growth defect. LPA acts on all bone cells including osteoblasts, that are responsible for bone formation, and osteoclasts, which are specialized cells that resorb bone. Read More

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Periostin interaction with discoidin domain receptor-1 (DDR1) promotes cartilage degeneration.

PLoS One 2020 24;15(4):e0231501. Epub 2020 Apr 24.

Division of Rheumatology, Department of Medicine, NYU Grossman School of Medicine, NYU Langone Orthopedic Hospital, New York, NY, United States of America.

Osteoarthritis (OA) is characterized by progressive loss of articular cartilage accompanied by the new bone formation and, often, a synovial proliferation that culminates in pain, loss of joint function, and disability. However, the cellular and molecular mechanisms of OA progression and the relative contributions of cartilage, bone, and synovium remain unclear. We recently found that the extracellular matrix (ECM) protein periostin (Postn, or osteoblast-specific factor, OSF-2) is expressed at high levels in human OA cartilage. Read More

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Protein kinase G1 regulates bone regeneration and rescues diabetic fracture healing.

JCI Insight 2020 05 7;5(9). Epub 2020 May 7.

Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Bone fractures are a major cause of morbidity and mortality, particularly in patients with diabetes, who have a high incidence of fractures and exhibit poor fracture healing. Coordinated expression of osteoblast-derived vascular endothelial growth factor (VEGF) and bone morphogenic proteins (BMPs) is essential for fracture repair. The NO/cGMP/protein kinase G (PKG) signaling pathway mediates osteoblast responses to estrogens and mechanical stimulation, but the pathway's role in bone regeneration is unknown. Read More

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Mesenchymal Stem Cell-Specific and Preosteoblast-Specific Ablation of TSC1 in Mice Lead to Severe and Slight Spinal Dysplasia, Respectively.

Biomed Res Int 2020 26;2020:4572687. Epub 2020 Mar 26.

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

Background: TSC1-related signaling plays a pivotal role in intramembranous and endochondral ossification processes during skeletogenesis. This study was aimed at determining the significance of the TSC1 gene at different stages of spinal development. . Read More

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January 2021

Postnatal Conditional Deletion of Bmal1 in Osteoblasts Enhances Trabecular Bone Formation Via Increased BMP2 Signals.

J Bone Miner Res 2020 08 14;35(8):1481-1493. Epub 2020 Apr 14.

Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China.

A large number of studies in recent years indicated the involvement of peripheral circadian clock in varied pathologies. However, evidence regarding how peripheral clocks regulate bone metabolism is still very limited. The present study aimed to investigate the direct role of Bmal1 (the key activator of peripheral circadian clock system) in vivo during bone developmental and remodeling stages using inducible osteoblast-specific Bmal1 knockout mice. Read More

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Deficiency of Macf1 in osterix expressing cells decreases bone formation by Bmp2/Smad/Runx2 pathway.

J Cell Mol Med 2020 01 11;24(1):317-327. Epub 2019 Nov 11.

Laboratory for Bone Metabolism, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China.

Microtubule actin cross-linking factor 1 (Macf1) is a spectraplakin family member known to regulate cytoskeletal dynamics, cell migration, neuronal growth and cell signal transduction. We previously demonstrated that knockdown of Macf1 inhibited the differentiation of MC3T3-E1 cell line. However, whether Macf1 could regulate bone formation in vivo is unclear. Read More

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January 2020

Responses of primary osteoblasts and osteoclasts from hemizygous β-globin knockout thalassemic mice with elevated plasma glucose to 1,25-dihydroxyvitamin D.

Sci Rep 2019 Sep 27;9(1):13963. Epub 2019 Sep 27.

Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.

β-thalassemia is often associated with hyperglycemia, osteoporosis and increased fracture risk. However, the underlying mechanisms of the thalassemia-associated bone loss remain unclear. It might result from abnormal activities of osteoblasts and osteoclasts, and perhaps prolonged exposure to high extracellular glucose. Read More

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September 2019

Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritis.

EBioMedicine 2019 Mar 26;41:538-555. Epub 2019 Feb 26.

Law Sau Fai Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong, China; School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address:

Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Read More

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Lysed Erythrocyte Membranes Promote Vascular Calcification.

Circulation 2019 04;139(17):2032-2048

Center for Cardiology, Cardiology I (R.G., A.H., E.B., I.D., T.M., K.S.), University Medical Center of the Johannes Gutenberg University Mainz, Germany.

Background: Intraplaque hemorrhage promotes atherosclerosis progression, and erythrocytes may contribute to this process. In this study we examined the effects of red blood cells on smooth muscle cell mineralization and vascular calcification and the possible mechanisms involved.

Methods: Erythrocytes were isolated from human and murine whole blood. Read More

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Loss of cyclin-dependent kinase 1 impairs bone formation, but does not affect the bone-anabolic effects of parathyroid hormone.

J Biol Chem 2018 12 26;293(50):19387-19399. Epub 2018 Oct 26.

From the Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan,

Bone mass is maintained by a balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Although recent genetic studies have uncovered various mechanisms that regulate osteoblast differentiation, the molecular basis of osteoblast proliferation remains unclear. Here, using an osteoblast-specific loss-of-function mouse model, we demonstrate that cyclin-dependent kinase 1 (Cdk1) regulates osteoblast proliferation and differentiation. Read More

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December 2018

E3-ubiquitin ligase NEDD4 enhances bone formation by removing TGFβ1-induced pSMAD1 in immature osteoblast.

Bone 2018 11 18;116:248-258. Epub 2018 Aug 18.

Department of Veterinary Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul, South Korea. Electronic address:

Neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) is an E3 ubiquitin ligase that regulates animal growth and development. To investigate the role of NEDD4 in skeletogenesis in vivo, we established immature osteoblast-specific 2.3-kb Collagen Type I Alpha 1 chain (Col1α1) promoter-driven Nedd4 transgenic (Nedd4-TG, Col1α1-Nedd4) mice and conditional knockout (Nedd4-cKO, Col1α1-Cre;Nedd4) mice. Read More

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November 2018

SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix.

Nat Commun 2018 07 19;9(1):2833. Epub 2018 Jul 19.

Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.

SP7/Osterix (OSX) is a master regulatory transcription factor that activates a variety of genes during differentiation of osteoblasts. However, the influence of post-translational modifications on the regulation of its transactivation activity is largely unknown. Here, we report that sirtuins, which are NAD(+)-dependent deacylases, regulate lysine deacylation-mediated transactivation of OSX. Read More

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FoxO1 expression in osteoblasts modulates bone formation through resistance to oxidative stress in mice.

Biochem Biophys Res Commun 2018 09 17;503(3):1401-1408. Epub 2018 Jul 17.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Chengdu, China; Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China. Electronic address:

Accumulation of reactive oxygen species (ROS) induced by oxidative stress (OS) affects cell survival, cell function and even results in cell death. As a major transcription factor of forkhead O (FoxOs) family, FoxO1 orchestrates multiple osteoblastic biological processes, thus regulating osteoblast physiology and bone metabolism. However, the outcome of osteoblast behaviors varies under different physiological and pathological conditions. Read More

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September 2018

Osterix regulates corticalization for longitudinal bone growth via integrin β3 expression.

Exp Mol Med 2018 07 18;50(7):1-11. Epub 2018 Jul 18.

Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju, Jeonbuk, 54896, Republic of Korea.

Corticalization, coalescence of trabecular bone into the metaphyseal cortex, is important for the longitudinal growth of long bones. However, little is known about the molecular mechanisms controlling corticalization. To understand the molecular mechanisms underlying corticalization, we analyzed osteoblast-specific Osterix-knockout mice (Col-OMT). Read More

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Defective autophagy in osteoblasts induces endoplasmic reticulum stress and causes remarkable bone loss.

Autophagy 2018 28;14(10):1726-1741. Epub 2018 Jul 28.

a The First Affiliated Hospital of Xi'an Jiaotong University; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education , Xi'an Jiaotong University Health Science Center , Xi'an , Shaanxi , China.

Macroautophagy/autophagy is a highly regulated process involved in the turnover of cytosolic components, however its pivotal role in maintenance of bone homeostasis remains elusive. In the present study, we investigated the direct role of ATG7 (autophagy related 7) during developmental and remodeling stages in vivo using osteoblast-specific Atg7 conditional knockout (cKO) mice. Atg7 cKO mice exhibited a reduced bone mass at both developmental and adult age. Read More

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October 2019

Sox2 is required for tumor development and cancer cell proliferation in osteosarcoma.

Oncogene 2018 08 10;37(33):4626-4632. Epub 2018 May 10.

Department of Microbiology, NYU School of Medicine, New York, NY, 10016, USA.

The stem cell transcription factor Sox2 is highly expressed in many cancers where it is thought to mark cancer stem cells (CSCs). In osteosarcomas, the most common bone malignancy, high Sox2 expression marks and maintains a fraction of tumor-initiating cells that show all the properties of CSC. Knockdown of Sox2 expression abolishes tumorigenicity and suppresses the CSC phenotype. Read More

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Osteoclast-secreted SLIT3 coordinates bone resorption and formation.

J Clin Invest 2018 04 5;128(4):1429-1441. Epub 2018 Mar 5.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Coupling is the process that links bone resorption to bone formation in a temporally and spatially coordinated manner within the remodeling cycle. Several lines of evidence point to the critical roles of osteoclast-derived coupling factors in the regulation of osteoblast performance. Here, we used a fractionated secretomic approach and identified the axon-guidance molecule SLIT3 as a clastokine that stimulated osteoblast migration and proliferation by activating β-catenin. Read More

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