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

Activated calcium-/calmodulin-dependent protein kinaseII (CaMKII) 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 CaMKII, and its relationship with the feedback loop of Indian hedgehog (Ihh) and Parathyroid-related peptide (PTHrP) in the temporomandibular joints (TMJs) OA. KN93, the competitive inhibitor of CaMKII, was added to the culture medium in vitro and was locally injected to rats TMJs (n=54, female) every other day for 4weeks from the beginning of the 5th and 9th week after installing of unilateral anterior crossbite (UAC), termed as 4wk+4wk and 8wk+4wk, accordingly. The RNA expression of CaMKII (1.49 +/- 0.09), CaMKII (3.36 +/- 0.20), Ihh (1.88 +/- 0.06) and PTHrP (1.87 +/- 0.12) was all enhanced, especially at 24dyn/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 4wk+4wk group in vivo. In the 8wk+4wk group, UAC upregulated the RNA expression of CaMKII (1.81 +/- 0.24), CaMKII (1.36 +/- 0.07) and Ihh (1.70 +/- 0.21), however, down-regulated PTHrP (0.53 +/- 0.04) (all P<.05), in consonance with the protein expression. All these changes were attenuated by KN93 (all P<.05). In conclusion, CaMKII took a role, via Ihh and PTHrP pathways, in promoting biomechanically induced TMJ chondrocytes differentiation, the initiation issue of UAC stimulated osteoarthritic changes in rodent TMJs. Inhibiting CaMKII is helpful to rescue the biomechanically stimulated cartilage degradation and prospective to be a target treatment of OA.