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

Abstract

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 reduced with the addition of TNF-α in vitro. Conclusion This study demonstrated that UC-MSC transplantation not only significantly improved the joint damage but also played a beneficial role in osteoporosis in CIA mice. Mechanistically, the improved osteogenic differentiation of CIA under UC-MSC treatment may be achieved by inhibition of TNF-α.

LncRNA HOXA‐AS2 positively regulates osteogenesis of mesenchymal stem cells through inactivating NF‐κB signalling

“…Previous studies have shown inflammation has a significant correlation with osteogenic differentiation . Nevertheless, the precise molecular basis has not been presented up to date.…”

“…Previous studies have shown inflammation has a significant correlation with osteogenic differentiation. [18][19][20] Nevertheless, the precise molecular basis has not been presented up to date. In the current study, we first examined the regulatory role of the primary inflammatory signalling NF-κB in osteogenesis, using gain or loss of NF-κB function experiments.…”

“…It is reported inflammation is significantly associated with osteogenic differentiation of MSCs. Furthermore, as is widely accepted that activation of inflammatory response has an inhibitory effect on osteogenesis . A recent study revealed TNFα‐induced NF‐κB activation upregulates microRNA‐150‐3p and inhibits osteogenesis of MSCs through downregulating β‐catenin .…”

“…Furthermore, as is widely accepted that activation of inflammatory response has an inhibitory effect on osteogenesis. [18][19][20] A recent study revealed TNFα-induced NF-κB activation upregulates microRNA-150-3p and inhibits osteogenesis of MSCs through downregulating β-catenin. 21 Another study showed decreased osteogenesis in mesenchymal stem cells derived from the aged mouse is associated with enhanced NF-κB activity.…”

LncRNA NKILA integrates RXFP1/AKT and NF‐κB signalling to regulate osteogenesis of mesenchymal stem cells

“…26 The activation of NF-κB can restrain osteogenesis. [22][23][24] However, the molecular basis by which NF-κB inhibits osteogenic differentiation is still unclear until now.…”