Osteoarthritis and cartilage · 2025
PTHrP signalling-dependent rehabilitative effects on CD90-expressing chondrocytes.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Xu Lingfeng, Zhang Yuejiao, Yang Hongxu, Zhang Jing, Liu Qian, Xu Jiali, Fan Peinan, Yu Jia, Zhou Peng, Xu Xiaojie, Huo Wanqiu, Zhang Mian, Lu Lei, Yu Shibin, Wu Yaoping, Wang Meiqing
Аннотация
OBJECTIVE: To investigate the parathyroid hormone-related peptide (PTHrP) nuclear localisation segment (PTHrP-NLS) and parathyroid hormone 1 receptor (PTH1R) signal-dependent rehabilitative effects of CD90+ chondrocytes (CD90-CCs) on degenerative temporomandibular joint (TMJ) cartilage.
DESIGN: Changes in PTHrP and PTH1R expression in CD90-CCs in TMJ cartilage in response to bilateral anterior elevation (BAE), which promotes TMJ cartilage thickening, were measured in female mice. A genetic modulation strategy was adopted. CD90-CCs were isolated from PTHrP-NLS conditional mutation (CD90-CreER;Pthlh84STOP) mice, PTH1R conditional mutation (CD90-CreER;Pth1r-/-) mice, human osteoarthritic knee cartilage (7 surgery operation donors) and rat osteoarthritic TMJ cartilage. These isolated CD90-CCs were cultured, amplified, and then injected into the experimental osteoarthritic TMJ, which was induced by the unilateral anterior crossbite (UAC) method, to evaluate the rehabilitative effect of the CD90-CCs (all, n = 6).
RESULTS: BAE increased the TMJ cartilage thickness and the expression of PTHrP and PTH1R. The cartilage thickening effect of BAE was retarded in PTHrP conditional mutation (CD90-CreER;Pthlh-/-) mice and CD90-CreER;Pth1r-/- mice. Local injections of CD90-CCs reversed 62.96% of the UAC-induced cartilage loss [95% CI: (46.93%, 78.99%)], whereas the rescue effect of CD90-CCs derived from CD90-CreER;Pthlh84STOP mice and CD90-CreER;Pth1r-/- mice was limited. CD90-CCs from osteoarthritic TMJ cartilage and osteoarthritic knee cartilage, both of which express PTHrP and PTH1R, also produced rehabilitative effects.
CONCLUSIONS: The restorative effects of CD90-CCs on cartilage are controlled by PTHrP-NLS and PTH1R signalling. Autologous infusion of sufficient numbers of expanded PTHrP and PTH1R dual signal-positive CD90-CCs could be a new strategy for treating joints with osteoarthritic cartilage.
DESIGN: Changes in PTHrP and PTH1R expression in CD90-CCs in TMJ cartilage in response to bilateral anterior elevation (BAE), which promotes TMJ cartilage thickening, were measured in female mice. A genetic modulation strategy was adopted. CD90-CCs were isolated from PTHrP-NLS conditional mutation (CD90-CreER;Pthlh84STOP) mice, PTH1R conditional mutation (CD90-CreER;Pth1r-/-) mice, human osteoarthritic knee cartilage (7 surgery operation donors) and rat osteoarthritic TMJ cartilage. These isolated CD90-CCs were cultured, amplified, and then injected into the experimental osteoarthritic TMJ, which was induced by the unilateral anterior crossbite (UAC) method, to evaluate the rehabilitative effect of the CD90-CCs (all, n = 6).
RESULTS: BAE increased the TMJ cartilage thickness and the expression of PTHrP and PTH1R. The cartilage thickening effect of BAE was retarded in PTHrP conditional mutation (CD90-CreER;Pthlh-/-) mice and CD90-CreER;Pth1r-/- mice. Local injections of CD90-CCs reversed 62.96% of the UAC-induced cartilage loss [95% CI: (46.93%, 78.99%)], whereas the rescue effect of CD90-CCs derived from CD90-CreER;Pthlh84STOP mice and CD90-CreER;Pth1r-/- mice was limited. CD90-CCs from osteoarthritic TMJ cartilage and osteoarthritic knee cartilage, both of which express PTHrP and PTH1R, also produced rehabilitative effects.
CONCLUSIONS: The restorative effects of CD90-CCs on cartilage are controlled by PTHrP-NLS and PTH1R signalling. Autologous infusion of sufficient numbers of expanded PTHrP and PTH1R dual signal-positive CD90-CCs could be a new strategy for treating joints with osteoarthritic cartilage.