PTHrP signalling-dependent rehabilitative effects on CD90-expressing chondrocytes.

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.