Calcium-/calmodulin-dependent protein kinase II in occlusion-induced degenerative cartilage of rat mandibular condyle
Calcium-/calmodulin-dependent protein kinase II in occlusion-induced degenerative cartilage of rat mandibular condyle
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钙/钙调蛋白依赖性蛋白激酶 II 在咬合诱导的大鼠下颌髁突退行性软骨中的作用
DOI：
10.1111/joor.12629
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Wang MQ
中科院分区：
文献类型：
--
作者：
Liu Q;Yang HX;Wang XH;Zhang M;Zhang J;Lu L;Xie MJ;Ren HT;Yu SB;Liu XD;Wang MQ
激活的钙/钙调蛋白依赖性蛋白激酶II(CaMKII)在促进软骨细胞从增殖状态向肥大前期状态转变中起重要作用，这可能在骨关节炎(OA)的发病机制中发挥作用。本研究的目的是探讨CaMKII在颞颌关节(TMJs)骨性关节炎(TMJs)中的作用及其与刺猬(IHH)和甲状旁腺相关肽(PTHrP)反馈环的关系。将CaMKII竞争性抑制剂KN93加入体外培养液中，从安装单侧前牙反牙合(UAC)后第5周和第9周开始隔天局部注射给大鼠TMJ(n=54，雌性)，连续4周，分别为4wk+4wk和8wk+4wk。CaMKIIα(1.49±0.09)、CaMKIIβ(3.36±0.20)、IHH(1.88±0.06)和PTHrP(1.87±0.12)的表达均增强，尤其是在24dyn/cm2时(P<0.05)，伴随着软骨基质表达下调，但软骨细胞分化标志物表达上调(P<0.05)。体内4wk+4wk组有相似之处。在8wk+4wk组，UAC上调CaMKIIα(1.81±0.24)、CaMKIIβ(1.36±0.07)和IHH(1.70±0.21)的RNA表达，下调PTHrP(0.53±0.04)(P<0.05)，与蛋白表达一致。所有这些变化均被KN93减弱(均P<；05)。综上所述，CaMKII通过IHH和PTHrP途径促进生物力学诱导的TMJ软骨细胞分化，UAC的启动问题刺激了啮齿动物TMJ的骨关节改变。抑制CaMKII有助于挽救生物力学刺激的软骨降解，有望成为骨性关节炎的靶向治疗方法。
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/cm2in vitro (allP< .05), accompanied with downregulated expression of cartilage matrix, but upregulated markers of chondrocytes differentiation (allP< 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) (allP< .05), in consonance with the protein expression. All these changes were attenuated by KN93 (allP< .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.