抄録
Human amniotic mesenchymal stem cells (hAMSCs) have attracted considerable attention due to their ability for the repair and regeneration of tissue. Hyaluronic acid (HA) could play important roles in articular cartilage repair treatment and inflammatory regulation. In this present study, the local intra-articular treatment of hAMSCs in combination with HA displayed a significant therapeutic effect in the iodoacetate-induced articular cartilage injure rat model. In comparison to hAMSCs alone or HA alone, the results of both magnetic resonance imaging (MRI) and immunofluorescence (IF) suggested that hAMSCs were able to colonize in the tissue of articilar cartiage injury after eight weeks of treatment. Furthmore, it could relieve articular swelling, reduce inflammation symptoms, improve clinical symptoms, and result in the cartilage tissue regeneration. Further analyses indicated that it could increase both collagen type II and glycosaminoglycan expression and accumulation in articular cartilage, significantly promote the levels of anti-inflammatory cytokines (IL-4, IL-10) and osteoprotegerin (OPG), and decreased the contents of pro-inflammatory cytokines (IL-6, IL-1beta, and TNF-alpha) in synovial fluid and blood serum samples. Subsequently, we tested the pro-differentiative effects of HA on chondrogenic differentiation of hAMSCs in vitro. Treatment of HA alone could induce glycosaminoglycan accumulation and type II collagen expression in hAMSCs. Furthermore, the mRNA and protein expression levels of chondrogenesis (Col2alpha1, Sox9, and ACAN) and stemness-related molecules (Sox2, Oct4, and Nanog) were significantly up-regulated in hAMSCs after HA treatment. In addition, the combinations of HA with chondrogenic inducer also resulted in a synergistic effects during chondrogenic differentiation of hAMSCs. Herein DLX5 and RASL11B played important role for chondrogenic differentiation of hAMSCs, and be implicated in TGF-beta signaling pathway.
Acknowledgement: Financial support from the National Natural Science Foundation of China (Nos. 81260278, 81460156, and 81660363), and Guizhou High-Level Innovative Talent Support Program (No. QKH-RC-20154028) are gratefully acknowledged.
Corresponding author J.H. Xiao (jianhuixiao@126.com)
