The immunoregulatory role of p21 in the development of the temporomandibular joint-osteoarthritis.
The immunoregulatory role of p21 in the development of the temporomandibular joint-osteoarthritis.
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p21在颞下颌关节骨关节炎发生发展中的免疫调节作用。
DOI：
10.1002/cre2.404
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发表时间：
2021-06
影响因子：
1.8
通讯作者：
Tanaka E
中科院分区：
文献类型：
--
作者：
Khurel-Ochir T;Izawa T;Iwasa A;Kano F;Yamamoto A;Tanaka E
我们的目的是确定细胞周期蛋白依赖的激酶抑制剂p21在机械应力影响的下颌骨软骨内稳态中的免疫调节作用。将10只C57BL/6野生型(WT)小鼠和10只8周龄p21−/−小鼠随机分为未治疗组和治疗组。在治疗组中，通过强迫张口对颞下颌关节施加机械应力，持续3 小时/天，连续7 天。用显微CT、组织学和免疫组织化学方法对解剖的TMJ进行评价。经机械应力处理的p21−/−髁突软骨下骨质破坏更严重，软骨层较薄，蛋白多糖面积较小；未经处理的WT和p21−/−髁突表面较光滑。免疫组织化学结果显示，p21β治疗组caspase-3、IL-1−/−、基质金属蛋白酶-9和基质金属蛋白酶-13阳性细胞数明显高于对照组，而aggrecan阳性细胞数较对照组明显减少。此外，机械应力作用下，p21−/−髁突的TUNEL阳性细胞数明显增加。我们的研究结果表明，在机械应力下，软骨细胞中的p21可能通过调控基质蛋白聚糖和基质金属蛋白酶-13的表达而参与基质合成的调节。因此，p21可能参与了TMJ骨性关节炎的发病机制。
We aimed to identify the immunoregulatory role of the cyclin‐dependent kinase inhibitor p21 in the homeostasis of mandibular condylar cartilage affected by mechanical stress. Ten C57BL/6 wild‐type (WT) and ten p21−/− mice aged 8 weeks were divided into the untreated and treated groups. In the treated groups, mechanical stress was applied to the temporomandibular joint (TMJ) through forced mouth opening for 3 hr/day for 7 days. The dissected TMJs were assessed using micro‐CT, histology, and immunohistochemistry. Treated p21−/− condyles with mechanical stress revealed more severe subchondral bone destruction, with thinner cartilage layers and smaller proteoglycan area relative to treated WT condyles; untreated WT and p21−/− condyles had smoother surfaces. Immunohistochemistry revealed significant increases in the numbers of caspase‐3, interleukin‐1β, matrix metalloprotease (MMP)‐9, and MMP‐13 positive cells, and few aggrecan positive cells, in treated p21−/− than in treated WT samples. Moreover, the number of TUNEL positive cells markedly increased in p21−/− condyles affected by mechanical stress. Our findings indicate that p21 in chondrocytes contributes to regulate matrix synthesis via the control ofm aggrecan and MMP‐13 expression under mechanical stress. Thus, p21 might regulate the pathogenesis of osteoarthritis in the TMJ.