β2-adrenergic signal transduction in mesenchymal stem cells (MSCs) induces subchondral bone loss in osteoarthritis (OA) of temporomandibular joints (TMJs). However, whether conditional deletion of β2-adrenergic receptor (Adrb2) in nestin+ MSCs can alleviate TMJ-OA development remains unknown. In this study, nestin-Cre mice were crossed with Adrb2 flox mice to generate mice lacking Adrb2 expression specifically in the nestin+ MSCs (Adrb2-/-), and TMJ-OA development in such mice was investigated. Adrb2 flox mice (Adrb2+/+) and Adrb2-/- mice were subjected to unilateral anterior crossbite (UAC), while mice in the control group were subjected to sham operation. Adrb2+/+ and Adrb2-/- mice in the control group showed no distinguishable phenotypic changes in body weight and length, mandibular condylar size, and other histomorphological parameters of the condylar subchondral bone. A significant increase in subchondral bone loss and cartilage degradation was observed in Adrb2+/+ UAC mice; the former was characterized by decreased bone mineral density, bone volume fraction, and trabecular plate thickness, and increased trabecular separation, osteoclast number and osteoclast surface, and pro-osteoclastic factor expression; the latter was characterized by decreased cartilage thickness, chondrocyte density, proteoglycan area, and collagen II and aggrecan expression, but increased matrix metalloproteinase and alkaline phosphatase expression and percentage area of calcified cartilage. Adrb2 deletion in nestin+ MSCs largely attenuated UAC-induced increase in condylar subchondral bone loss, cartilage degradation, and aberrant calcification at the osteochondral interface. Thus, Adrb2-expressing MSCs in the condylar subchondral bone play an important role in TMJ-OA progression and may serve as novel therapeutic targets for TMJ-OA.

中文翻译：

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间充质干细胞中 Adrb2 的条件缺失减轻了颞下颌关节的骨关节炎样缺陷

间充质干细胞 (MSC) 中的 β2-肾上腺素能信号转导诱导颞下颌关节 (TMJ) 骨关节炎 (OA) 的软骨下骨丢失。然而，巢蛋白+ MSCs中β2-肾上腺素能受体（Adrb2）的条件性缺失是否可以减轻TMJ-OA的发展仍然未知。在这项研究中，将 nestin-Cre 小鼠与 Adrb2 flox 小鼠杂交以产生在 nestin+ MSCs (Adrb2-/-) 中特异性缺乏 Adrb2 表达的小鼠，并研究了此类小鼠的 TMJ-OA 发育。Adrb2 flox小鼠(Adrb2+/+)和Adrb2-/-小鼠进行单侧前牙反咬合(UAC)，对照组小鼠进行假手术。对照组中的 Adrb2+/+ 和 Adrb2-/- 小鼠在体重和长度、下颌髁突大小、和髁突软骨下骨的其他组织形态学参数。在 Adrb2+/+ UAC 小鼠中观察到软骨下骨丢失和软骨退化显着增加；前者的特点是骨密度、骨体积分数和骨小梁板厚度降低，骨小梁分离、破骨细胞数量和破骨细胞表面增加，促破骨细胞因子表达增加；后者的特点是软骨厚度、软骨细胞密度、蛋白多糖面积和胶原蛋白 II 和聚集蛋白聚糖表达减少，但基质金属蛋白酶和碱性磷酸酶表达增加，钙化软骨面积百分比增加。巢蛋白+间充质干细胞中的 Adrb2 缺失在很大程度上减弱了 UAC 诱导的髁突软骨下骨丢失、软骨退化、和骨软骨界面的异常钙化。因此，髁突软骨下骨中表达 Adrb2 的 MSCs 在 TMJ-OA 进展中起重要作用，并可作为 TMJ-OA 的新治疗靶点。