Publications by authors named "Weiwen Zhu"

17 Publications

  • Page 1 of 1

Exosomal miR-100-5p inhibits osteogenesis of hBMSCs and angiogenesis of HUVECs by suppressing the BMPR2/Smad1/5/9 signalling pathway.

Stem Cell Res Ther 2021 Jul 13;12(1):390. Epub 2021 Jul 13.

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Background: Nontraumatic osteonecrosis of the femoral head (NONFH) is a common, progressive, and refractory orthopaedic disease. Decreased osteogenesis and angiogenesis are considered the main factors in the pathogenesis of NONFH. We aimed to figure out whether exosomes and exosomal miRNA from necrotic bone tissues of patients with NONFH are involved in the pathogenesis of NONFH and reveal the underlying mechanisms.

Methods: RT-PCR and western blotting (WB) were used to detect the expression of osteogenic, adipogenic, and angiogenic markers. ALP staining and Alizarin Red S (ARS) staining were used to evaluate osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Oil Red O staining was performed to assess the adipocyte deposition. A tube formation assay was used to study angiogenesis of human umbilical vascular endothelial cells (HUVECs). H&E staining and immunohistochemistry (IHC) staining were used to detect the effect of the NONFH exosomes in vivo. MicroRNA sequencing was conducted to identify potential regulators in the NONFH exosomes. The target relationship between miR-100-5p and BMPR2 was predicted and confirmed by a dual luciferase reporter assay and WB.

Results: The NONFH exosomes reduced the osteogenic differentiation of hBMSCs and angiogenesis of HUVECs. In addition, the injection of the NONFH exosomes caused thinning and disruption of bone trabeculae in the femoral heads of rats. MiR-100-5p expression was upregulated in the NONFH exosomes and inhibited the osteogenesis of hBMSCs and angiogenesis of HUVECs by targeting BMPR2 and suppressing the BMPR2/SMAD1/5/9 signalling pathway. Silencing miR-100-5p expression rescued the reduction in osteogenesis and angiogenesis caused by the NONFH exosomes by activating the BMPR2/SMAD1/5/9 signalling pathway.

Conclusion: The NONFH exosomal miR-100-5p can lead to NONFH-like damage by targeting BMPR2 and suppressing the BMPR2/SMAD1/5/9 signalling pathway, which may be involved in the pathophysiological mechanisms of nontraumatic osteonecrosis of the femoral head (NONFH).
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http://dx.doi.org/10.1186/s13287-021-02438-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278698PMC
July 2021

Abnormal macrophage polarization impedes the healing of diabetes-associated tooth sockets.

Bone 2021 02 26;143:115618. Epub 2020 Aug 26.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China. Electronic address:

Patients with poorly controlled type 2 diabetes mellitus (T2DM) often experience delayed tooth extraction socket (TES) healing. Delayed healing is often associated with an aberrant inflammatory response orchestrated by either M1 pro-inflammatory or M2 anti-inflammatory macrophages. However, the precise mechanism for the attenuated TES healing remains unclear. Here we used diet-induced T2DM mice as a model to study TES. Compared with the control group, the T2DM group showed delayed TES healing and diminished expression of osteogenic and angiogenic genetic profiles. Meanwhile, we detected a more inflammatory profile, with more M1 macrophages and TNF-α expression and less M2 macrophages and PPARγ expression, in TES in the T2DM group when compared to control mice. In vitro co-culture models showed that M1 macrophages inhibited the osteogenic capacity of bone marrow stromal cells and the angiogenic capacity of endothelial cells while M2 macrophages showed an opposite effect. In addition, we constructed a gelatin/β-TCP scaffold with IL-4 to induce macrophage transformation towards M2 polarization. In vitro analyses of the hybrid scaffold revealed sustained release of IL-4 and a phenotype switch to M2 macrophages. Finally, we demonstrated that sustained IL-4 release significantly increased expression of osteogenic and angiogenic genetic profiles and improved TES healing in T2DM mice. Together, we report that increased M1 and decreased M2 macrophage polarization may be responsible for delayed TES healing in T2DM patients through abnormal expression of TNF-α and PPARγ. This imbalance negatively influences osteogenesis and angiogenesis, two of the most important biological factors in bone wound healing. Enhancing M2 macrophage polarization with IL-4 delivery system may represent a potential strategy for promoting the healing of TES in T2DM patients.
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http://dx.doi.org/10.1016/j.bone.2020.115618DOI Listing
February 2021

CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells.

Cell Death Dis 2020 04 27;11(4):293. Epub 2020 Apr 27.

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Non-traumatic osteonecrosis of the femoral head (ONFH) is clinically a devastating and progressive disease without an effective treatment. Mesenchymal stem cells (MSCs) transplantation has been used to treat ONFH in early stage, but the failure rate of this therapy is high due to the reduced osteogenic differentiation and migration of the transplanted MSCs related with pathological bone tissues. However, the mechanism responsible for this decrease is still unclear. Therefore, we assume that the implanted MSCs might be influenced by signals delivered from pathological bone tissue, where the exosomes might play a critical role in this delivery. This study showed that exosomes from ONFH bone tissues (ONFH-exos) were able to induce GC-induced ONFH-like damage, in vivo and impair osteogenic differentiation and migration of MSCs, in vitro. Then, we analyzed the differentially expressed proteins (DEPs) in ONFH-exos using proteomic technology and identified 842 differentially expressed proteins (DEPs). On the basis of gene ontology (GO) enrichment analysis of DEPs, fold-changes and previous report, cell adhesion-related CD41 (integrin α2b) was selected for further investigation. Our study showed that the CD41 (integrin α2b) was distinctly decreased in ONFH-exos, compared to NOR-exos, and downregulation of CD41 could impair osteogenic differentiation and migration of the MSCs, where CD41-integrin β3-FAK-Akt-Runx2 pathway was involved. Finally, our study further suggested that CD41-affluent NOR-exos could restore the glucocorticoid-induced decline of osteogenic differentiation and migration in MSCs, and prevent GC-induced ONFH-like damage in rat models. Taken together, our study results revealed that in the progress of ONFH, exosomes from the pathological bone brought about the failure of MSCs repairing the necrotic bone for lack of some critical proteins, like integrin CD41, and prompted the progression of experimentally induced ONFH-like status in the rat. CD41 could be considered as the target of early diagnosis and therapy in ONFH.
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http://dx.doi.org/10.1038/s41419-020-2496-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184624PMC
April 2020

[Progranulin aggravates postmenopausal osteoporosis in ovariectomized mice].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019 Aug;35(8):714-720

Department of Orthopedics, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. *Corresponding author, E-mail:

Objective To investigate the effect of progranulin (PGRN) on osteoporosis in ovariectomized mice. Methods PGRN-knockout (PGRN) and wild-type mice were ovariectomized to induce postmenopausal osteoporosis models. Next, the bone tissues in all mice were scanned by Micro-CT and three-dimensional reconstruction was performed to detect the micro-structure, followed by trabecula data analysis. The morphology and osteoclasts in the bone tissues of PGRN and wild-type mice were observed by HE staining and TRAP staining, respectively. The expression of receptor activator for nuclear factor-κB ligand (RANKL), tumor necrosis factor α (TNF-α) and P65 were detected by immunohistochemistry. The expression of TRAP mRNA in the mice was measured using fluorescence quantitative PCR and the protein expression of MMP9, MMP14, P65 was detected by Western blot analysis. Results Bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th) in the PGRN group were significantly higher than those in the wild-type group, while the trabecular separation (Tb.S) in the PGRN group was in the contrary. The degree of osteoporosis was less severe and number of osteoclasts in the PGRN mice were reduced, likewise, RANKL, TNF-α, MMP9, MMP14 and P65 as well as TRAP mRNA were down-regulated in the PGRN group compared with the wild-type group. Conclusion PGRN aggravates the postmenopausal osteoporosis in ovariectomized mice.
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August 2019

Gene expression profiling of the bone trabecula in patients with osteonecrosis of the femoral head by RNA sequencing.

J Biochem 2019 Dec;166(6):475-484

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, 1 Yi Xue Yuan Road, Yu Zhong District, Chongqing 400016, China.

Early diagnosis and treatment of osteonecrosis of the femoral head (ONFH) is challenging. Bone trabecula play a vital role in the severity and progression of ONFH. In the present study, the investigators used gene expression profiling of bone trabecula to investigate gene alterations in ONFH patients. Osteonecrotic bone trabecula (ONBT) such as necrosis, fibrosis, and lacuna were confirmed by histological examination in the patients. The adjacent 'normal' bone trabecula (ANBT) did not show any pathological changes. Gene sequencing data revealed that although ANBT showed no significant histological changes, alteration of mRNA profiling in ANBT was observed, similar to that in ONBT. Our results indicated that the alteration of mRNA profiling in ANBT may cause normal bone tissue to develop into necrotic bone. RNA-seq data indicated that 2,297 differentially abundant mRNAs were found in the ONBT group (1,032 upregulated and 1,265 downregulated) and 1,523 differentially abundant mRNAs in the ANBT group (744 upregulated and 799 downregulated) compared with the healthy control group. Gene ontology (GO) enrichment analysis suggested that fatty acid metabolism and degradation were the main zones enriched with differentially expressed genes (DEG). Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis indicated that peroxisome proliferator-activated receptor γ (PPAR-γ) pathway was the most significantly regulated pathway. Lipocalin-2 (LCN2), an osteoblast-enriched secreted protein, was significantly decreased in ONBT suggesting that downregulation of LCN2 might affect lipid metabolism and lead to hyperlipidemia, and thus promote pathogenesis of ONFH.
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http://dx.doi.org/10.1093/jb/mvz060DOI Listing
December 2019

Severe Fever With Thrombocytopenia Syndrome Virus-Induced Macrophage Differentiation Is Regulated by miR-146.

Front Immunol 2019 15;10:1095. Epub 2019 May 15.

Center for Public Health Research, Medical School, Nanjing University, Nanjing, China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with a high mortality rate in humans, which is caused by SFTS virus (SFTSV), a novel phlebovirus in the family, is tick borne and endemic in Eastern Asia. Previous study found that SFTSV can infect and replicate in macrophages and . However, the role of macrophages in virus replication and the potential pathogenic mechanisms of SFTSV in macrophage remain unclear. In this study, we provided evidence that the SFTSV infection drove macrophage differentiation skewed to M2 phenotype, facilitated virus shedding, and resulted in viral spread. We showed evidence that miR-146a and b were significantly upregulated in macrophages during the SFTSV infection, driving the differentiation of macrophages into M2 cells by targeting STAT1. Further analysis revealed that the elevated miR-146b but not miR-146a was responsible for IL-10 stimulation. We also found that SFTSV increased endogenous miR-146b-induced differentiation of macrophages into M2 cells mediated by viral non-structural protein (NSs). The M2 skewed differentiation of macrophages may have important implication to the pathogenesis of SFTS.
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http://dx.doi.org/10.3389/fimmu.2019.01095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529556PMC
September 2020

Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw.

FASEB J 2019 04 9;33(4):5208-5219. Epub 2019 Jan 9.

Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a detrimental side effect of the long-term administration of bisphosphonates. Although macrophages were reported to be an important mediator of BRONJ, the detailed potential mechanism of BRONJ remains unclear. Here, we reported an elevated TLR-4 expression in macrophages under action of zoledronic acid (ZA), resulting in enhanced M1 macrophage polarization and decreased M2 macrophage polarization both in vitro and in vivo. After inhibiting the TLR-4 signaling pathway, the activation of the TLR-4/NF-κB signaling pathway and the induction of NF-κB nuclear translocation and production of proinflammatory cytokines by ZA were suppressed in macrophages, thereby inhibiting M1 macrophage polarization. By utilizing the TLR-4 mice, development of BRONJ was markedly ameliorated, and M1 macrophages were significantly attenuated in the extraction socket tissues in the TLR-4 mice. Importantly, the systemic administration of the TLR-4 inhibitor TAK-242 improved the wound healing of the extraction socket and decreased the incidence rate of BRONJ. Taken together, our findings suggest that TLR-4-mediated macrophage polarization participates in the pathogenesis of BRONJ in mice, and TLR-4 may be a potential target for the prevention and therapeutic treatment of BRONJ.-Zhu, W., Xu, R., Du, J., Fu, Y., Li, S., Zhang, P., Liu, L., Jiang, H. Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw.
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http://dx.doi.org/10.1096/fj.201801791RRDOI Listing
April 2019

Concentration-dependent effects of rapamycin on proliferation, migration and apoptosis of endothelial cells in human venous malformation.

Exp Ther Med 2018 Dec 19;16(6):4595-4601. Epub 2018 Sep 19.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

Rapamycin has been reported to be immunosuppressive and anti-proliferative towards vascular endothelial and smooth muscle cells. The purpose of the present study was to investigate the effects of rapamycin on the biological behaviors of endothelial cells that have been separated from the deformed vein in human venous malformation (VM). Cellular morphology was observed using inverted microscopy. An MTT assay was performed to measure the cell viability at different concentrations of rapamycin and different time points. Cell apoptosis and migration were detected using a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay and a wound-healing assay, respectively. At 48 and 72 h, rapamycin inhibited proliferation of human VM endothelial cells, with the effects becoming more pronounced with increasing concentration. Only rapamycin at a concentration of 1,000 ng/ml had a significant effect at 24 h in repressing proliferation. At 48 h, compared with the blank group, the majority of cells maintained a clear nuclear boundary and a regular shape following treatment with 1 ng/ml rapamycin; 10 and 100 ng/ml rapamycin caused desquamation and rounded shape; and 1,000 ng/ml rapamycin caused even more marked desquamation, rounded shape and necrosis. Rapamycin at concentrations of 1, 10, 100 and 1,000 ng/ml reduced cell viability, increased the number of apoptotic cells and suppressed the migration capacity of human VM endothelial cells, and the effects became more pronounced with increasing concentration, when compared with the blank group. These findings provide evidence that rapamycin induces apoptosis and inhibits proliferation and migration of human VM endothelial cells in a concentration-dependent manner.
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http://dx.doi.org/10.3892/etm.2018.6782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257489PMC
December 2018

microRNA-31 inhibition partially ameliorates the deficiency of bone marrow stromal cells from cleidocranial dysplasia.

J Cell Biochem 2019 06 3;120(6):9472-9486. Epub 2018 Dec 3.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

Background: Cleidocranial dysplasia (CCD) in humans is an autosomal-dominant skeletal dysplasia caused by heterozygous mutations of the runt-related transcription factor 2 (RUNX2) and significantly increases the risk of osteoporosis. Increasing evidence demonstrates that the dysfunction of bone marrow stromal cells from CCD patients (BMSCs-CCD) contributes to the bone deficiency, but the characteristics of BMSCs-CCD and the mechanisms that underlie their properties remain undefined.

Methods: The clinical manifestations of three CCD patients were collected and the mutations of RUNX2 were analyzed. The properties of proliferation, osteogenesis, stemness, and senescence of BMSCs-CCD were compared with that of BMSCs from healthy donors. The expression of microRNA-31 ( miR-31) between BMSCs-CCD and BMSCs was measured and lentivirus-carried miR-31 inhibitor was used to determine the role of miR-31 in BMSCs-CCD both in vitro and in vivo. The molecular mechanisms underlying RUNX2-miR31 and miR-31 targeting stemness and senescence of BMSCs-CCD were also explored.

Results: We identified two mutation sites of RUNX2 via exome sequencing from 2 of 3 Chinese CCD patients with typical clinical presentations. Compared with BMSCs from healthy donors, BMSCs-CCD displayed significantly attenuated proliferation, osteogenesis and stemness, and enhanced senescence. Meanwhile, miR-31 knockdown could ameliorate these deficiency phenotypes of BMSCs-CCD by regulating SATB2, BMI1, CDKN, and SP7. Mechanistically, RUNX2 directly repressed miR-31 expression, and therefore RUNX2 haploinsufficiency in CCD leading to miR-31 upregulation contributed to the deficiency of BMSCs-CCD. miR-31 inhibition in BMSCs-CCD showed enhanced osteogenesis through heterotopic subcutaneous implantation in the nude mice.

Conclusions: Our results show the functional deficiencies of BMSCs-CCD and a potential role of miR-31 in BMSCs-CCD deficiencies. The application of miR-31 inhibitor in BMSCs-CCD might lend hope for developing BMSC-based therapeutic approaches against CCD-associated skeletal diseases.
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http://dx.doi.org/10.1002/jcb.28223DOI Listing
June 2019

HDAC8, A Potential Therapeutic Target, Regulates Proliferation and Differentiation of Bone Marrow Stromal Cells in Fibrous Dysplasia.

Stem Cells Transl Med 2019 02 13;8(2):148-161. Epub 2018 Nov 13.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, People's Republic of China.

Fibrous dysplasia (FD) is a disease of postnatal skeletal stem cells caused by activating mutations of guanine nucleotide-binding protein alpha-stimulating activity polypeptide (GNAS). FD is characterized by high proliferation and osteogenesis disorder of bone marrow stromal cells (BMSCs), resulting in bone pain, deformities, and fractures. The cAMP-CREB pathway, which is activated by GNAS mutations, is known to be closely associated with the occurrence of FD. However, so far there is no available targeted therapeutic strategy for FD, as a critical issue that remains largely unknown is how this pathway is involved in FD. Our previous study revealed that histone deacetylase 8 (HDAC8) inhibited the osteogenic differentiation of BMSCs via epigenetic regulation. Here, compared with normal BMSCs, FD BMSCs exhibited significantly high proliferation and weak osteogenic capacity in response to HDAC8 upregulation and tumor protein 53 (TP53) downregulation. Moreover, inhibition of cAMP reduced HDAC8 expression, increased TP53 expression and resulted in the improvement of FD phenotype. Importantly, HDAC8 inhibition prevented cAMP-induced cell phenotype and promoted osteogenesis in nude mice that were implanted with FD BMSCs. Mechanistically, HDAC8 was identified as a transcriptional target gene of CREB1 and its transcription was directly activated by CREB1 in FD BMSCs. In summary, our study reveals that HDAC8 associates with FD phenotype and demonstrates the mechanisms regulated by cAMP-CREB1-HDAC8 pathway. These results provide insights into the molecular regulation of FD pathogenesis, and offer novel clues that small molecule inhibitors targeting HDAC8 are promising clinical treatment for FD. Stem Cells Translational Medicine 2019;8:148&14.
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http://dx.doi.org/10.1002/sctm.18-0057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344909PMC
February 2019

MicroRNA-31a-5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment.

Aging Cell 2018 08 12;17(4):e12794. Epub 2018 Jun 12.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

The alteration of age-related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age-related bone loss. Here, we observed that the level of microRNA-31a-5p (miR-31a-5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain-of-function and knockdown approach to delineate the roles of miR-31a-5p in osteogenic differentiation by assessing the decrease of special AT-rich sequence-binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence-associated heterochromatin foci (SAHF). Notably, expression of miR-31a-5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs-derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR-31a-5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR-31a-5p, we observed that, in the bone marrow microenvironment, inhibition of miR-31a-5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR-31a-5p acts as a key modulator in the age-related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age-related osteoporosis.
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http://dx.doi.org/10.1111/acel.12794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052401PMC
August 2018

Metabolic analysis of osteoarthritis subchondral bone based on UPLC/Q-TOF-MS.

Anal Bioanal Chem 2016 Jun 13;408(16):4275-86. Epub 2016 Apr 13.

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Osteoarthritis (OA), one of the most widespread musculoskeletal joint diseases among the aged, is characterized by the progressive loss of articular cartilage and continuous changes in subchondral bone. The exact pathogenesis of osteoarthritis is not completely clear. In this work, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) in combination with multivariate statistical analysis was applied to analyze the metabolic profiling of subchondral bone from 42 primary osteoarthritis patients. This paper described a modified two-step method for extracting the metabolites of subchondral bone from primary osteoarthritis patients. Finally, 68 metabolites were identified to be significantly changed in the sclerotic subchondral bone compared with the non-sclerotic subchondral bone. Taurine and hypotaurine metabolism and beta-alanine metabolism were probably relevant to the sclerosis of subchondral bone. Taurine, L-carnitine, and glycerophospholipids played a vital regulation role in the pathological process of sclerotic subchondral bone. In the sclerotic process, beta-alanine and L-carnitine might be related to the increase of energy consumption. In addition, our findings suggested that the intra-cellular environment of sclerotic subchondral bone might be more acidotic and hypoxic compared with the non-sclerotic subchondral bone. In conclusion, this study provided a new insight into the pathogenesis of subchondral bone sclerosis. Our results indicated that metabolomics could serve as a promising approach for elucidating the pathogenesis of subchondral bone sclerosis in primary osteoarthritis. Graphical Abstract Metabolic analysis of osteoarthritis subchondral bone.
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http://dx.doi.org/10.1007/s00216-016-9524-xDOI Listing
June 2016

[Leptin inhibits the differentiation of RAW264.7 macrophages into osteoclasts via depressing the expression of PPARγ].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2015 Feb;31(2):145-8

Department of Orthopedics, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.

Objective: To investigate the effects of leptin on the differentiation of RAW264.7 cells into osteoclasts induced by soluble receptor activator of nuclear factor-κB ligand (sRANKL) and its possible mechanism.

Methods: The effects of leptin on the differentiation from osteoclast precursor cells into osteoclasts were detected by tartrate-resistant acid phosphatase (TRAP) staining. The mRNA expressions of TRAP and peroxisome proliferator-activated receptor γ (PPARγ) in osteoclast precursor cells were measured by real-time quantitative PCR (qRT-PCR). The protein expressions of TRAP and PPARγ were detected by Western blotting.

Results: Compared with sRANKL treatment group, the differentiation from osteoclast precursor cells into osteoclasts was significantly inhibited in sRANKL combined with leptin treatment groups. Additionally, the mRNA and protein expressions of both TRAP and PPARγ significantly decreased in sRANKL combined with leptin treatment groups compared with the sRANKL treatment alone. Furthermore, the expression of PPARγ was reduced in a dose-dependent manner.

Conclusion: Leptin could inhibit the differentiation of RAW264.7 cells into osteoclasts via inhibiting the expression of PPARγ.
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February 2015

Double triangular prism filter based on the optical-readout method in a microelectromechanical infrared imaging system.

Appl Opt 2012 Feb;51(5):669-75

School of Optoelectronics, Beijing Institute of Technology, China.

This paper presents a novel filtering method with a double triangular prism in an optical-readout thermal imaging system. First, the working principle of this system is described in detail, followed by the analysis of sensitivity. Then, infrared images of hands are obtained. On the basis of the analysis, it is concluded that this filtering method, whose noise equivalent temperature difference (NETD) can reach 145 mK, is effective in obtaining high-quality images. Finally, comparing the filtering method with a knife-edge filter, we can draw the conclusion that the filtering method can effectively improve image quality (the value of NETD is less than that of a knife-edge filter).
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http://dx.doi.org/10.1364/AO.51.000669DOI Listing
February 2012

[Sequence and evolutionary analysis of VP1 gene of ovine rotavirus NT].

Wei Sheng Wu Xue Bao 2009 Aug;49(8):1055-62

Key Lab of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.

Objective: The ovine rotavirus strain NT isolated from diarrhea lamb in China was considered as a promising vaccine strain. Based on the VP1 gene was one of the important structural proteins of rotavirus, we studied on the evolutional characteristics of VP1.

Methods: According to the published conservative sequences of VP1 genes, we designed a pair of specific primers for cloning and sequencing of VP1 gene.

Results: Sequencing result showed that the VP1 gene was 3,302 bp in length and the deduced protein was 1,088 aa. Comparison of amino acid sequences revealed that the ORV-NT shared 77.3% - 98.4% similarities with other group A rotaviruses. Furthermore, sequence alignment analysis manifested that amino acid variations mainly occurred in the non-functional regions of VP1 protein. Phylogenetic analysis of VP1 protein showed that the OVR-NT was grouped in the bovine rotavirus clusters, indicating a closer relationship between them. Evolutionary distance of nucleotide sequence and amino acid sequence among VP1 genes of different rotaviruses were calculated, respectively. Analysis of synonymous mutation rate and Non-synonymous mutation rate demonstrated that synonymous substitution was the major pattern of variation in the process of evolution.

Conclusion: This was the first report on sequencing and evolutionary distance analysis of VP1 gene of ORV-NT.
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August 2009

Whole genome sequencing of lamb rotavirus and comparative analysis with other mammalian rotaviruses.

Virus Genes 2009 Apr 13;38(2):302-10. Epub 2009 Feb 13.

Key Lab of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 7 Beitucheng West Road, Chaoyang District, Beijing, 100029, China.

Rotavirus (RV) epidemiological surveys with molecular analysis of various strains are required for gastroenteritis control and prevention. The lamb rotavirus strain NT, isolated from a diarrhea lamb in China, is considered as a promising vaccine strain. The whole genome of the lamb-NT strain was determined by sequence analysis. Sequence identity and phylogenetic analysis defined the lamb-NT strain as group A, genotype G10P[15]/NSP4[A]/SG1 strain. Comparative genomic analysis of the lamb-NT strain and 17 reference strains reveals that gene reassortments between rotaviruses circulating in different species occurred. Alignment of protein sequences of the genes shows some variations in the important functional regions of VP3 and VP4. These variations are related to host range restriction, virulence, and other potential characters of rotaviruses. Besides, this study also makes a significant foundation for the study of genetic classification, epidemiology, and antigenic diversity of rotaviruses on the molecular level.
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http://dx.doi.org/10.1007/s11262-009-0332-7DOI Listing
April 2009

Development of an enzyme-linked immunosorbent assay for the pyrethroid insecticide cyhalothrin.

J Agric Food Chem 2006 Jul;54(15):5284-91

Department of Ecology and Environmental Sciences, College of Resource and Environment and College of Natural Sciences, China Agricultural University, Beijing, 100094, People's Republic of China.

A competitive enzyme-linked immunosorbent assay (ELISA) was developed for detection of the pyrethroid insecticide cyhalothrin. Three haptens with an amine or propanoic acid terminus were synthesized and then conjugated with bovine serum albumin to give immunogens. Eight polyclonal antisera produced by rabbits were screened for titers and affinity using three different coating antigens. The antiserum CWB-C had the highest affinity with cyhalothrin and a low affinity with fenvalerate, fenpropathrin, deltamethrin, and fluvalinate. The half-maximum inhibition concentration for cyhalothrin was 37.2 microg/L, and the limit of detection was 4.7 microg/L. The recoveries of different concentrations of cyhalothrin (0.1-2500 microg/L) from fortified tap water, well water, and wastewater samples as determined with the ELISA were 81-114%.
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http://dx.doi.org/10.1021/jf0607009DOI Listing
July 2006