Osteoarthritis（OA）is a degenerative joint disorder commonly encountered in clinical practice,and is the leading cause of disability in elderly people.Due to the poor self-healing capacity of articular cartilage and ...Osteoarthritis（OA）is a degenerative joint disorder commonly encountered in clinical practice,and is the leading cause of disability in elderly people.Due to the poor self-healing capacity of articular cartilage and lack of specific diagnostic biomarkers,OA is a challenging disease with limited treatment options.Traditional pharmacologic therapies such as acetaminophen,non-steroidal anti-inflammatory drugs,and opioids are effective in relieving pain but are incapable of reversing cartilage damage and are frequently associated with adverse events.Current research focuses on the development of new OA drugs（such as sprifermin/recombinant human fibroblast growth factor-18,tanezumab/monoclonal antibody againstβ-nerve growth factor）,which aims for more effectiveness and less incidence of adverse effects than the traditional ones.Furthermore,regenerative therapies（such as autologous chondrocyte implantation（ACI）,new generation of matrix-induced ACI,cell-free scaffolds,induced pluripotent stem cells（iPS cells or iPSCs）,and endogenous cell homing）are also emerging as promising alternatives as they have potential to enhance cartilage repair,and ultimately restore healthy tissue.However,despite currently available therapies and research advances,there remain unmet medical needs in the treatment of OA.This review highlights current research progress on pharmacologic and regenerative therapies for OA including key advances and potential limitations.展开更多
PIP5k1βis crucial to the generation of phosphotidylinosotol(4,5)P2.PIP5k1βparticipates in numerous cellular activities,such as B cell and platelet activation,cell phagocytosis and endocytosis,cell apoptosis,and cyto...PIP5k1βis crucial to the generation of phosphotidylinosotol(4,5)P2.PIP5k1βparticipates in numerous cellular activities,such as B cell and platelet activation,cell phagocytosis and endocytosis,cell apoptosis,and cytoskeletal organization.In the present work,we aimed to examine the function of PIP5k1βin osteoclastogenesis and osteogenesis to provide promising strategies for osteoporosis prevention and treatment.We discovered that PIP5k1β deletion in mice resulted in obvious bone loss and that PIP5k1β was highly expressed during both osteoclast and osteoblast differentiation.Deletion of the gene was found to enhance the proliferation and migration of bone marrow-derived macrophage-like cells to promote osteoclast differentiation.PIP5k1β-/-osteoclasts exhibited normal cytoskeleton architecture but stronger resorption activity.PIP5kip deficiency also promoted activation of mitogen-activated kinase and Akt signaling,enhanced TRAF6 and c-Fos expression,facilitated the expression and nuclear translocation of NFATC1,and upregulated Grb2 expression,thereby accelerating osteoclast differentiation and function.Finally,PIP5k1β enhanced osteoblast differentiation by upregulating master gene expression through triggering smad1/5/8 signaling.Therefore,PIP5k1βmodulates bone homeostasis and remodeling.展开更多
Complement receptor 2 （CR2/CD21） is predominantly expressed on the surface of mature B cells where it forms part of a coreceptor complex that functions, in part, to modulate B-cell receptor signal strength. CR2/CD21...Complement receptor 2 （CR2/CD21） is predominantly expressed on the surface of mature B cells where it forms part of a coreceptor complex that functions, in part, to modulate B-cell receptor signal strength. CR2/CD21 expression is tightly regulated throughout B-cell development such that CR2/CD21 cannot be detected on pre-B or terminally differentiated plasma cells. CR2/CD21 expression is upregulated at B-cell maturation and can be induced by IL-4 and CD40 signaling pathways. We have previously characterized elements in the proximal promoter and first intron of CR2/CD21 that are involved in regulating basal and tissue-specific expression. We now extend these analyses to the CR2/CD21 core promoter. We show that in mature B cells, CR2/~D21 transcription proceeds from a focused TSS regulated by a non-consensus TATA box, an initiator element and a downstream promoter element. Furthermore, occupancy of the general transcriptional machinery in pre-B versus mature B-cell lines correlate with CR2/CD21 expression level and indicate that promoter accessibility must switch from inactive to active during the transitional B-cell window.展开更多
Chronic obstructive pulmonary disease （COPD） is characterized by chronic irreversible inflammation and progressive decline in lung function. While smoking and other environmental agents （e.g., air pollutants） are ...Chronic obstructive pulmonary disease （COPD） is characterized by chronic irreversible inflammation and progressive decline in lung function. While smoking and other environmental agents （e.g., air pollutants） are common causes of COPD, the major challenges in managing this condition are the persistent inflammation and functional deterioration which are not reversed by removal of precipitating agents （e.g., smoking cessation） or treatment with anti-inflammatory agents.展开更多
Developing the radiographic images from two to three-dimensional, finite element analysis(FEA) technology can set up the model, predicting diagnosis, treatment design, as well as surgical plan. FEA provides an accurat...Developing the radiographic images from two to three-dimensional, finite element analysis(FEA) technology can set up the model, predicting diagnosis, treatment design, as well as surgical plan. FEA provides an accurate three-dimensional finite element biomechanical study in osteonecrosis of femoral head(ONFH). The papers in the latest 5 years related to femoral head osteonecrosis and finite element analysis application are concentrated on. We summarize the latest research progress and problems, including the applied research carried out in the femoral head osteonecrosis clinical cases,innovational skills, so as to point out the direction of future research in FEA.展开更多
Systemic inflammation is a feature of chronic obstructive pulmo- nary disease （COPD）. Defects in T cell-mediated anti-inflamma- tory pathways such as cytotoxic T lymphocyte antigen-4 （CTLA- 4） may promote damaging...Systemic inflammation is a feature of chronic obstructive pulmo- nary disease （COPD）. Defects in T cell-mediated anti-inflamma- tory pathways such as cytotoxic T lymphocyte antigen-4 （CTLA- 4） may promote damaging inflammation. This study provides novel data implicating the impaired induction of an anti-inflam- matory molecule, CTLA-4 in the elevated inflammation observed in COPD patients. Low induction of CTLA-4 in COPD patients paralleled increased markers of systemic inflammation ex vivo and increased T-cell responses to a bacterial superantigen, staphylo- coccal enterotoxin-B （SEB） in vitro. This mechanism may explain the increased inflammation in COPD patients.展开更多
基金supported in part by NHMRCa grant from the Natural Science Foundation of China(NSFCNo. 81228013)
文摘Osteoarthritis（OA）is a degenerative joint disorder commonly encountered in clinical practice,and is the leading cause of disability in elderly people.Due to the poor self-healing capacity of articular cartilage and lack of specific diagnostic biomarkers,OA is a challenging disease with limited treatment options.Traditional pharmacologic therapies such as acetaminophen,non-steroidal anti-inflammatory drugs,and opioids are effective in relieving pain but are incapable of reversing cartilage damage and are frequently associated with adverse events.Current research focuses on the development of new OA drugs（such as sprifermin/recombinant human fibroblast growth factor-18,tanezumab/monoclonal antibody againstβ-nerve growth factor）,which aims for more effectiveness and less incidence of adverse effects than the traditional ones.Furthermore,regenerative therapies（such as autologous chondrocyte implantation（ACI）,new generation of matrix-induced ACI,cell-free scaffolds,induced pluripotent stem cells（iPS cells or iPSCs）,and endogenous cell homing）are also emerging as promising alternatives as they have potential to enhance cartilage repair,and ultimately restore healthy tissue.However,despite currently available therapies and research advances,there remain unmet medical needs in the treatment of OA.This review highlights current research progress on pharmacologic and regenerative therapies for OA including key advances and potential limitations.
基金This work was supported by grants from the National Natural Science Foundation of China(81830078,81772347,and 81572123)Science and Technology Commission of Shanghai Municipality(19XD1434100 and 16430723500)+1 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(2016131A)Shanghai Jiao Tong University-The Chinese University of Hong Kong joint Research Collaboration Fund.
文摘PIP5k1βis crucial to the generation of phosphotidylinosotol(4,5)P2.PIP5k1βparticipates in numerous cellular activities,such as B cell and platelet activation,cell phagocytosis and endocytosis,cell apoptosis,and cytoskeletal organization.In the present work,we aimed to examine the function of PIP5k1βin osteoclastogenesis and osteogenesis to provide promising strategies for osteoporosis prevention and treatment.We discovered that PIP5k1β deletion in mice resulted in obvious bone loss and that PIP5k1β was highly expressed during both osteoclast and osteoblast differentiation.Deletion of the gene was found to enhance the proliferation and migration of bone marrow-derived macrophage-like cells to promote osteoclast differentiation.PIP5k1β-/-osteoclasts exhibited normal cytoskeleton architecture but stronger resorption activity.PIP5kip deficiency also promoted activation of mitogen-activated kinase and Akt signaling,enhanced TRAF6 and c-Fos expression,facilitated the expression and nuclear translocation of NFATC1,and upregulated Grb2 expression,thereby accelerating osteoclast differentiation and function.Finally,PIP5k1β enhanced osteoblast differentiation by upregulating master gene expression through triggering smad1/5/8 signaling.Therefore,PIP5k1βmodulates bone homeostasis and remodeling.
文摘Complement receptor 2 （CR2/CD21） is predominantly expressed on the surface of mature B cells where it forms part of a coreceptor complex that functions, in part, to modulate B-cell receptor signal strength. CR2/CD21 expression is tightly regulated throughout B-cell development such that CR2/CD21 cannot be detected on pre-B or terminally differentiated plasma cells. CR2/CD21 expression is upregulated at B-cell maturation and can be induced by IL-4 and CD40 signaling pathways. We have previously characterized elements in the proximal promoter and first intron of CR2/CD21 that are involved in regulating basal and tissue-specific expression. We now extend these analyses to the CR2/CD21 core promoter. We show that in mature B cells, CR2/~D21 transcription proceeds from a focused TSS regulated by a non-consensus TATA box, an initiator element and a downstream promoter element. Furthermore, occupancy of the general transcriptional machinery in pre-B versus mature B-cell lines correlate with CR2/CD21 expression level and indicate that promoter accessibility must switch from inactive to active during the transitional B-cell window.
文摘Chronic obstructive pulmonary disease （COPD） is characterized by chronic irreversible inflammation and progressive decline in lung function. While smoking and other environmental agents （e.g., air pollutants） are common causes of COPD, the major challenges in managing this condition are the persistent inflammation and functional deterioration which are not reversed by removal of precipitating agents （e.g., smoking cessation） or treatment with anti-inflammatory agents.
基金Natural Science Foundation of Guangdong Provincegrant number:2014A030310214+3 种基金Science and Technology Project of Guangdong Provincegrant number:2014A020221041the Medical Science and Technology Foundation of Guangdong Provincegrant number:A2015039
文摘Developing the radiographic images from two to three-dimensional, finite element analysis(FEA) technology can set up the model, predicting diagnosis, treatment design, as well as surgical plan. FEA provides an accurate three-dimensional finite element biomechanical study in osteonecrosis of femoral head(ONFH). The papers in the latest 5 years related to femoral head osteonecrosis and finite element analysis application are concentrated on. We summarize the latest research progress and problems, including the applied research carried out in the femoral head osteonecrosis clinical cases,innovational skills, so as to point out the direction of future research in FEA.
文摘Systemic inflammation is a feature of chronic obstructive pulmo- nary disease （COPD）. Defects in T cell-mediated anti-inflamma- tory pathways such as cytotoxic T lymphocyte antigen-4 （CTLA- 4） may promote damaging inflammation. This study provides novel data implicating the impaired induction of an anti-inflam- matory molecule, CTLA-4 in the elevated inflammation observed in COPD patients. Low induction of CTLA-4 in COPD patients paralleled increased markers of systemic inflammation ex vivo and increased T-cell responses to a bacterial superantigen, staphylo- coccal enterotoxin-B （SEB） in vitro. This mechanism may explain the increased inflammation in COPD patients.
