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

Abstract

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 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 CaMKII α (1.49 ± 0.09), CaMKII β (3.36 ± 0.20), Ihh (1.88 ± 0.06) and PTHrP (1.87 ± 0.12) was all enhanced, especially at 24 dyn/cm 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 CaMKII α (1.81 ± 0.24), CaMKII β (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.

MTORC1 coordinates the autophagy and apoptosis signaling in articular chondrocytes in osteoarthritic temporomandibular joint

“…The condylar cartilage contains four layers, i.e., the superficial fibrous, proliferative, pre-hypertrophic and hypertrophic zones. Consistent with our previous results [6], UAC treatment induced OA-like lesions in the TMJ condylar cartilage in rats, such as reduced matrix production and marked cartilage loss in pre-hypertrophic and hypertrophic zones ( Figure 1(a), Figure S1(a)). Apoptosis was enhanced as demonstrated by increased numbers of cleaved CASP3-, CASP12-, DDIT3-, and TUNEL-positive chondrocytes during the entire UAC experimental time, i.e., from 2 to 20 wk ( Figure 1(b-g), Figure S1(b-e)).…”

“…Temporomandibular joint (TMJ), which relates biomechanically to dental occlusion, is a site frequently insulted by OA [4]. We recently reported that fluid flow shear stress (FFSS) induced TMJ chondrocyte death in vitro [5][6][7]. We also developed an in vivo abnormal dental occlusion termed unilateral anterior cross (UAC) model and demonstrated that it induced chondrocyte death and OA-like lesions in TMJ cartilage in rats and mice [7][8][9][10][11].…”

MiR-21-5p regulates extracellular matrix degradation and angiogenesis in TMJOA by targeting Spry1

“…Our experiments aimed to investigate the possible mechanism of action of miR-21-5p in condylar cartilage inflammatory degeneration by establishing a UAC mouse model to induce cartilage structural dysfunction and using IL-1β to induce the inflammatory state of MCCs. In recent years, the UAC model has been widely used to induce TMJOA, that is, to change the occlusal load distribution and induce OA through experimental unilateral anterior cross occlusion, leading to the loss of subchondral bone in the TMJ [20][21][22]. In vivo experiments confirmed that UAC induced TMJ cartilage degeneration and found that MMP-13, VEGF and IL-1β were upregulated.…”

MiR-21-5p regulates extracellular matrix degradation and angiogenesis in TMJOA by targeting Spry1.

“…Then, the expression of VEGF in the mimic + U0126 group was significantly lower than that in the mimic group (Fig. 8d) In recent years, the UAC model has been widely used to induce TMJOA, that is, to change the occlusal load distribution and induce OA through experimental unilateral anterior cross occlusion, leading to the loss of subchondral bone in the TMJ [20,21,22]. In vitro experiments have used the inflammationinducing factor IL-1β, which is closely related to bone and cartilage loss in OA, and many studies have demonstrated that the MMP induction by IL-1β is mediated by the ERK-MAPK signalling pathway [24,25,26].…”