title: Duhuo Jisheng Decoction promotes chondrocyte proliferation through accelerated G1/S transition in osteoarthritis.
abstract: Duhuo Jisheng Decoction (DHJSD), a well known traditional Chinese folk medicine, is used for eliminating stagnation, removing blood stasis, promoting blood circulation and alleviating pain; it is commonly used for the treatment of various diseases, including osteoarthritis (OA). However, the molecular mechanisms behind the therapeutic effects of OA remain unclear. In the present study, the effects of DHJSD on the morphology of articular cartilage and the G1/S cell cycle progression in chondrocytes, as well as the underlying mechanisms, were investigated. A total of 27 two‑month‑old male Sprague Dawley rats were randomly divided into 3 groups: the control group (no papain-induced OA; received an equivalent amount of saline only), the model group (papain-induced OA; received an equivalent amount of saline only) and the DHJSD group [papain-induced OA; received a clinical oral dose of DHJSD (9.3 g/kg/day)]. After 8 consecutive weeks of treatment, the morphological changes in articular cartilage were observed under an optical microscope and by transmission electron microscopy (TEM) and the mRNA and protein expression levels of cyclin D1, CDK4, CDK6, retinoblastoma protein (Rb) and p16 were measured by RT‑PCR and immunohistochemistry, respectively. Treatment with DHJSD significantly improved the arrangement of collagen fibers in the articular cartilage, as well as its structure and reduced cell degeneration compared with the model group. The mRNA and protein expression levels of cyclin D1, CDK4, CDK6 and Rb in the DHJSD‑treated group were significantly increased compared with those in the model group, whereas p16 expression was significantly downregulated. Taken together, these results indicate that DHJSD treatment promotes chondrocyte proliferation by promoting the G1/S checkpoint transition in the cell cycle and by upregulating the expression of cyclin D1, CDK4, CDK6 and Rb and downregulating the expression of p16 and this may, in part, explain its clinical efficacy in the treatment of osteoarthritis.
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Wu
authors.forename: Wenlie
authors.initials: W
authors.lastname: Chen
authors.forename: Huailing
authors.initials: H
authors.lastname: Fan
authors.forename: Chunsong
authors.initials: C
authors.lastname: Zheng
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Chu
authors.forename: Ruhui
authors.initials: R
authors.lastname: Lin
authors.forename: Jinxia
authors.initials: J
authors.lastname: Ye
authors.forename: Huifeng
authors.initials: H
authors.lastname: Xu
authors.forename: Xihai
authors.initials: X
authors.lastname: Li
authors.forename: Yunmei
authors.initials: Y
authors.lastname: Huang
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Ye
authors.forename: Xianxiang
authors.initials: X
authors.lastname: Liu
authors.forename: Mingxia
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D019938:Cyclin D1 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D016193:G1 Phase / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019938:Cyclin D1; D051361:Cyclin-Dependent Kinase 6