Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner.
Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner.
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Osteoking 通过 TGF-β/smad 依赖性方式减缓 DMM 诱导的骨关节炎小鼠模型中的软骨退化
DOI：
10.3389/fphar.2021.678810
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发表时间：
2021
影响因子：
5.6
通讯作者：
Tong P
中科院分区：
文献类型：
--
作者：
Ling H;Zeng Q;Ge Q;Chen J;Yuan W;Xu R;Shi Z;Xia H;Hu S;Jin H;Wang P;Tong P
骨关节炎（OA）是一种以软骨变性为特征的常见疾病。近年来，中药治疗软骨退化的疗效显著，副作用轻，引起了人们的广泛关注。骨疗是一种长期用于骨关节炎治疗的中药方剂。然而，骨形成的确切机制尚未完全阐明。在本研究中，引入了内侧半月板失稳（DMM）诱导的OA小鼠作为野生型动物模型。给药8周后，进行组织形态学测量、OARSI评分、步态分析、显微ct和Col2、MMP-13、TGFβRII和pSmad-2的免疫组化染色，以评估骨固定在体内的软骨保护作用。然后进行进一步的体外实验来检测成骨对软骨细胞的影响。本研究构建并引入TGF-β riicol2er转基因小鼠，验证成骨是否通过TGF-β信号通路发挥其抗oa作用。结果表明，在野生型DMM小鼠中，成骨治疗改善了oa表型，包括软骨退化、软骨下骨硬化和步态异常。成骨治疗后，Col2、TGFβRII、pSmad-2表达上调，MMP-13表达下调。在体外，IL-1β处理后，MMP-13和ADAMTS5 mRNA表达降低，Aggrecan、COL2和tgf - β rii mRNA表达上调。SB505124的额外治疗抵消了成骨对原发性软骨细胞的积极影响。在TGFβRIICol2ER小鼠中，观察到自发的OA样表型，骨巩固治疗未能逆转OA的自发进展。综上所述，成骨可通过TGF-β信号通路减缓软骨退化和减轻软骨下骨硬化，从而改善骨性关节炎的进展。
Osteoarthritis (OA) is a common disease characterized by cartilage degeneration. In recent years much attention has been paid to Traditional Chinese Medicine (TCM) since its treatments have shown efficacy for ameliorating cartilage degradation with mild side effects. Osteoking is a TCM prescription that has long been used in OA treatment. However, the exact mechanism of Osteoking are not fully elucidated. In the current study, destabilization of the medial meniscus (DMM)-induced OA mice was introduced as a wild type animal model. After 8 weeks of administration of Osteoking, histomorphometry, OARSI scoring, gait analysis, micro-CT, and immunohistochemical staining for Col2, MMP-13, TGFβRII and pSmad-2 were conducted to evaluate the chondroprotective effects of Osteoking in vivo. Further in vitro experiments were then performed to detect the effect of Osteoking on chondrocytes. TGFβRIICol2ER transgenic mice were constructed and introduced in the current study to validate whether Osteoking exerts its anti-OA effects via the TGF-β signaling pathway. Results demonstrated that in wild type DMM mice, Osteoking ameliorated OA-phenotype including cartilage degradation, subchondral bone sclerosis, and gait abnormality. Col2, TGFβRII, and pSmad-2 expressions were also found to be up-regulated after Osteoking treatment, while MMP-13 was down-regulated. In vitro, the mRNA expression of MMP-13 and ADAMTS5 decreased and the mRNA expression of Aggrecan, COL2, and TGFβRII were up-regulated after the treatment of Osteoking in IL-1β treated chondrocytes. The additional treatment of SB505124 counteracted the positive impact of Osteoking on primary chondrocytes. In TGFβRIICol2ER mice, spontaneous OA-liked phenotype was observed and treatment of Osteoking failed to reverse the OA spontaneous progression. In conclusion, Osteoking ameliorates OA progression by decelerating cartilage degradation and alleviating subchondral bone sclerosis partly via the TGF-β signaling pathway.
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影响因子：
4.9
作者：
Wang M;Sampson ER;Jin H;Li J;Ke QH;Im HJ;Chen D
通讯作者：
Chen D
影响因子：
--
作者：
Aigner, T;Vornehm, SI;Bayliss, MT
通讯作者：
Bayliss, MT
DOI：
10.1155/2017/5190986
发表时间：
2017
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Li L;Liu H;Shi W;Liu H;Yang J;Xu D;Huang H;Wu L
通讯作者：
Wu L
影响因子：
27.4
作者：
Neogi T;Nevitt M;Niu J;Sharma L;Roemer F;Guermazi A;Lewis CE;Torner J;Javaid K;Felson D
通讯作者：
Felson D
影响因子：
8.8
作者：
Fuseya, Satoshi;Yamamoto, Katsumi;Kawamata, Mikito
通讯作者：
Kawamata, Mikito