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Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF- α

作者:Chang Liu, Huayong Zhang, Xiaojun Tang, Ruihai Feng, Genhong Yao, Weiwei Chen, Wenchao Li, Jun Liang, Xuebing Feng, Lingyun Sun · 发表于:Stem Cells International · 年份:2018 · DOI:10.1155/2018/4069032 · 被引用次数:40 · 研究领域:Mesenchymal stem cell research、Osteoarthritis Treatment and Mechanisms、Bone and Joint Diseases

Objective . To investigate the effects of umbilical cord mesenchymal stem cell (UC-MSC) transplantation on joint damage and osteoporosis in collagen-induced arthritis (CIA) mice and to explore the mechanisms by which UC-MSCs modulate the osteogenic differentiation. Methods . CIA mice were divided into the following treated groups: UC-MSC transplantation group, antitumor necrosis factor- (TNF-) α group, and zoledronic acid (ZA) group. Microcomputed tomography (micro-CT) was used to analyze the bone morphology parameters. Osteogenic differentiation of treated CIA mice was determined. Bone marrow mesenchymal stem cells (BM-MSCs) from CIA mice were treated with TNF- α in vitro to explore their effects on osteogenesis. Results . The arthritis score was significantly reduced in the UC-MSC transplantation and anti-TNF- α -treated CIA groups, compared with control mice ( P < 0.001 ). Micro-CT showed that CIA mice developed osteoporosis at 12 weeks after immunization. The bone morphology parameters were partially improved in UC-MSC-treated CIA mice. Impaired osteogenic differentiation functions were indicated by decreased ALP activity ( P < 0.001 ) and reduced mRNA and protein levels of osteogenic marker genes ( P < 0.05 ) in CIA mice compared with DBA/1 mice. UC-MSC treatment significantly upregulated the impaired osteogenic differentiation ability in CIA mice. Meanwhile, the serum TNF- α level was decreased significantly in the UC-MSC group. The osteogenesis was...