Background/Purpose:  To investigate the effects of umbilical cord-mesenchymal stem cell (UC-MSC) transplantation on joint damage and systemic osteoporosis in collagen induced arthritis (CIA) mice.

Methods: DBA/1 male mice were induced to CIA models by injecting type II Collagen (CII). Then CIA mice were divided into four groups, including CIA control group, UC-MSC transplantation group, anti-tumor necrosis factor alpha (anti-TNFα) treatment group and zoledronic acid (ZA) treatment group. The CIA mice were treated for 8 weeks. Arthritis score of CIA mice were evaluated every 3 days. Micro computed tomography (micro-CT) was used to analyze the bone morphology parameters. Bone marrow mesenchymal stem cells (BMMSCs) were isolated and cultured in the osteogenic medium. Osteogenic differentiation was determined by alkaline phosphatase (ALP) staining and ALP activity on day 7. The expression of the osteogenic markers ALP, Osterix and type I collagen (COL-I) were analyzed by RT-PCR and western bloton day 7 and day 14 respectively. Moreover, bone marrow monocytes (BMMs) were isolated and induced to osteoclast (OC) in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-КB ligand. OC differentiation was determined by tartrate-resistant acid phosphatase (TRAP) staining and mRNA levels of nuclear factor of activated T cells (NFAT)2 and osteoprotegerin (OPG).

Results: The arthritis score was significantly reduced in UC-MSC transplantation and anti-TNFα treated CIA group compared with control mice. Micro-CT showed that the BMD, trabecular bone volume/total volume (BV/TV) and trabecular number (Tb.N) of the femur were significantly decreased in CIA mice, compared with that in DBA/1 mice. H&E staining also showed a reduced Tb.N in CIA mice. Whereas these parameters were partially improved in UC-MSCs treated CIA mice compared with control mice. Impaired osteogenic differentiation functions were shown by decreased ALP activity, reduced gene and protein levels of osteogenic marker genes in CIA mice compared with DBA/1 mice. UC-MSCs treatment significantly upregulated the osteogenic differentiation ability in CIA mice. Moreover, TRAP staining and OC counting showed that OC number was increased in CIA mice compared to that in DBA/1 mice. The NFAT2 mRNA levels were elevated in CIA mice compared to that in DBA/1 mice, however the OPG mRNA levels were decreased in CIA mice. UC-MSC treatment downregulated the enhanced OC differentiation in CIA mice.

Conclusion: The present study demonstrated that CIA mice developed osteoporosis. UC-MSCs transplantation not only improved the joint damage significantly but also played a positive role in osteoporosis in CIA mice. The osteogenic differentiation ability of BMMSCs in CIA mice was impaired. The OC differentiation function of BMMs in CIA mice was enhanced. UC-MSCs transplantation could upregulate the osteogenic differentiation and downregulate the OC differentiation in CIA mice. Thus, we provide strong evidence that MSCs ameliorate inflammation-induced systemic bone loss in CIA mice by upregulating osteogenic differentiation and reducing OC differentiation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/regulatory-mechanisms-of-mesenchymal-stem-cell-transplantation-on-systemic-osteoporosis-in-collagen-induced-arthritis-mice/