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
This study investigated the effects of SIRT1 gene knock-out on osteoarthritis in mice, and the possible roles of SREBP2 protein and the PI3K/AKT signaling pathway in the effects. Mice were randomly divided into a norm...This study investigated the effects of SIRT1 gene knock-out on osteoarthritis in mice, and the possible roles of SREBP2 protein and the PI3K/AKT signaling pathway in the effects. Mice were randomly divided into a normal group and a SIRT1 gene knock-out group（6 mice in each group）. In these groups, one side of the knee anterior cruciate ligament was traversed, and the ipsilateral medial meniscus was cut to establish an osteoarthritis model of knee joint. The countralateral synovial bursa was cut out, serving as controls. The knee joint specimens were then divided into four groups： SIRT1^（＋/＋） control group（group A, n=6）; SIRT1^（＋/＋） osteoarthritis group（group B, n=6）; SIRT1^（–/–） control group（group C, n=6）; SIRT1^（–/–） osteoarthritis group（group D, n=6）. HE staining, Masson staining, Safranin O-Fast Green staining and Van Gieson staining were used to observe the morphological changes in the articular cartilage of the knee. Immunohistochemical staining was employed to detect the expression of SIRT1, SREBP2, VEGF, AKT, HMGCR and type Ⅱ collagen proteins. SA-β-gal staining was utilized to evaluate chondrocyte aging. The results showed clear knee joint cartilage destruction and degeneration in the SIRT1^（–/–） osteoarthritis group. The tidal line was twisted and displaced anteriorly. Type Ⅱ collagen was destroyed and distributed unevenly. Compared with the SIRT1^（＋/＋） osteoarthritis group and SIRT1^（–/–） control group, SIRT1 protein expression was not obviously changed in the SIRT1^（–/–） osteoarthritis group（P〉0.05）, while the expression levels of the SREBP2, VEGF and HMGCR proteins were significantly increased（P〈0.05） and the levels of AKT and type Ⅱ collagen proteins were significantly decreased（P〈0.05）. SIRT1 gene knock-out may aggravate cartilage degeneration in osteoarthritis by activating the SREBP2 protein-mediated PI3K/AKT signalling pathway, suggesting that SIRT1 gene may play a protective role again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supported by grants from the National Natural Science Foundation of China(No.81272032)the Research and Development Projects of Shenzhen of China(Nos.JCYJ20150403091443275)
文摘This study investigated the effects of SIRT1 gene knock-out on osteoarthritis in mice, and the possible roles of SREBP2 protein and the PI3K/AKT signaling pathway in the effects. Mice were randomly divided into a normal group and a SIRT1 gene knock-out group（6 mice in each group）. In these groups, one side of the knee anterior cruciate ligament was traversed, and the ipsilateral medial meniscus was cut to establish an osteoarthritis model of knee joint. The countralateral synovial bursa was cut out, serving as controls. The knee joint specimens were then divided into four groups： SIRT1^（＋/＋） control group（group A, n=6）; SIRT1^（＋/＋） osteoarthritis group（group B, n=6）; SIRT1^（–/–） control group（group C, n=6）; SIRT1^（–/–） osteoarthritis group（group D, n=6）. HE staining, Masson staining, Safranin O-Fast Green staining and Van Gieson staining were used to observe the morphological changes in the articular cartilage of the knee. Immunohistochemical staining was employed to detect the expression of SIRT1, SREBP2, VEGF, AKT, HMGCR and type Ⅱ collagen proteins. SA-β-gal staining was utilized to evaluate chondrocyte aging. The results showed clear knee joint cartilage destruction and degeneration in the SIRT1^（–/–） osteoarthritis group. The tidal line was twisted and displaced anteriorly. Type Ⅱ collagen was destroyed and distributed unevenly. Compared with the SIRT1^（＋/＋） osteoarthritis group and SIRT1^（–/–） control group, SIRT1 protein expression was not obviously changed in the SIRT1^（–/–） osteoarthritis group（P〉0.05）, while the expression levels of the SREBP2, VEGF and HMGCR proteins were significantly increased（P〈0.05） and the levels of AKT and type Ⅱ collagen proteins were significantly decreased（P〈0.05）. SIRT1 gene knock-out may aggravate cartilage degeneration in osteoarthritis by activating the SREBP2 protein-mediated PI3K/AKT signalling pathway, suggesting that SIRT1 gene may play a protective role again
