Nell-1 regulates fibrocartilage stem cells and alleviates temporomandibular joint osteoarthritis progression by inhibiting hedgehog pathway

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Nel-like molecule-1 (Nell-1) could prevent the damage of cartilage in osteoarthritis (OA), including temporomandibular joint osteoarthritis (TMJOA), though, the definite mechanism of the process is unclear. Fibrocartilage stem cells (FCSCs) were discovered in the temporomandibular joint (TMJ), and were associated with the TMJ health and disease. However, little information is available on the effect of Nell-1 on FCSCs fate in TMJOA progression. Methods In this study, TMJOA was induced in rabbits through collagenase injection. 8 weeks after injection, the left and right joints of the rabbits were injected with AAV9-CMV-Nell-1 and AAV9 vector virus supernatant respectively. FCSCs were isolated, cultured, and transfected with recombinant AdNell-1. Histology staining, immunofluorescence staining, micro-CT, qRT-PCR and western blot were applied to detect the condition of FCSCs and condyles in vitro and in vivo. Results In the collagenase injection group, we observed histological changes consistent with OA, meanwhile, the expression of Nell-1 was decreased, but Indian hedgehog (Ihh) and Sonic hedgehog (Shh) were significantly elevated in FCSCs and condylar cartilage. Further in vitro and in vivo analyses revealed that Nell-1 markedly reduced Ihh and Shh. In addition, Nell-1 induced the chondrogenic differentiation of FCSCs by stimulating the expression of Collagen II, Aggr

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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