Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Implant Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710004, China.
The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, 471003, China.
J Bone Miner Metab. 2024 Sep;42(5):529-537. doi: 10.1007/s00774-024-01524-4. Epub 2024 Jul 9.
Articular cartilage is the major affected tissue during the development of osteoarthritis (OA) in temporomandibular joint (TMJ). The core circadian rhythm molecule Bmal1 regulates chondrocyte proliferation, differentiation and apoptosis; however, its roles in condylar cartilage function and in TMJ OA have not been fully elucidated.
TMJ OA mouse model was induced by unilateral anterior crossbite (UAC) and Bmal1 protein expression in condylar cartilage were examined by western blot analysis. To determine the role of Bmal1 in TMJ OA, we generated cartilage-specific Bmal1 conditional knockout (cKO) mice (Bmal1 mice) and hematoxylin and eosin staining, toluidine blue and Safranin O/fast green, immunohistochemistry, TUNEL assay, real-time PCR analysis and Western blot assay were followed.
Bmal1 expression was reduced in condylar cartilage in a TMJ OA mouse model induced by UAC. The Bmal1 cKO mice displayed decreased cartilage matrix synthesis, reduced chondrocyte proliferation, increased chondrocyte hypertrophy and apoptosis as well as the upregulation of YAP expression in TMJ condylar cartilage.
We demonstrated that Bmal1 was essential for TMJ tissue homeostasis and loss-of-function of Bmal1 in chondrocytes leads to the development of TMJ OA.
关节软骨是颞下颌关节（TMJ）骨关节炎（OA）发展过程中主要受影响的组织。核心生物钟分子 Bmal1 调节软骨细胞的增殖、分化和凋亡；然而，其在髁突软骨功能和 TMJ OA 中的作用尚未完全阐明。
通过单侧前牙反合（UAC）诱导 TMJ OA 小鼠模型，通过 Western blot 分析检查髁突软骨中 Bmal1 蛋白的表达。为了确定 Bmal1 在 TMJ OA 中的作用，我们生成了软骨特异性 Bmal1 条件性敲除（cKO）小鼠（Bmal1 小鼠），并进行了组织学染色、甲苯胺蓝和番红 O/固绿染色、免疫组织化学、TUNEL 检测、实时 PCR 分析和 Western blot 分析。
UAC 诱导的 TMJ OA 小鼠模型中髁突软骨中 Bmal1 的表达减少。Bmal1 cKO 小鼠的 TMJ 髁突软骨中软骨基质合成减少、软骨细胞增殖减少、软骨细胞肥大和凋亡增加以及 YAP 表达上调。
我们证明了 Bmal1 对于 TMJ 组织稳态是必不可少的，并且软骨细胞中 Bmal1 的功能丧失会导致 TMJ OA 的发展。
