Calcium‐/calmodulin‐dependent protein kinase II in occlusion‐induced degenerative cartilage of rat mandibular condyle

Summary Activated calcium‐/calmodulin‐dependent protein kinaseII (Ca MK II) is important to promote chondrocytes from proliferative to pre‐hypertrophic state, which probably plays a role in osteoarthritis ( OA ), a widespread degeneration disease with enhanced aberrant chondrocyte differentiation. Our aim was to detect the role of Ca MK II, and its relationship with the feedback loop of Indian hedgehog (Ihh) and Parathyroid‐related peptide (PTHrP) in the temporomandibular joints ( TMJ s) OA . KN 93, the competitive inhibitor of Ca MK II, was added to the culture medium in vitro and was locally injected to rats TMJ s (n = 54, female) every other day for 4 weeks from the beginning of the 5th and 9th week after installing of unilateral anterior crossbite ( UAC ), termed as 4 wk+4 wk and 8 wk+4 wk, accordingly. The RNA expression of Ca MK II α (1.49 ± 0.09), Ca MK II β (3.36 ± 0.20), Ihh (1.88 ± 0.06) and PTH rP (1.87 ± 0.12) was all enhanced, especially at 24 dyn/cm 2 in vitro (all P < .05), accompanied with downregulated expression of cartilage matrix, but upregulated markers of chondrocytes differentiation (all P < 0.05). Similarity was observed in the 4 wk+4 wk group in vivo. In the 8 wk+4 wk group, UAC upregulated the RNA expression of Ca MK II α (1.81 ± 0.24), Ca MK II β (1.36 ± 0.07) and Ihh (1.70 ± 0.21), however, down‐regulated PTH rP (0.53 ± 0.04) (all P < .05), in consonance with the protein expression. All these changes were attenuated by KN 93 (all P < .05). In conclusion, Ca MK II took a role, via Ihh and PTH rP pathways, in promoting biomechanically induced TMJ chondrocytes differentiation, the initiation issue of UAC stimulated osteoarthritic changes in rodent TMJ s. Inhibiting Ca MK II is helpful to rescue the biomechanically stimulated cartilage degradation and prospective to be a target treatment of OA .