Wang Pengzhen, Liu Jian, Zhang Shaoheng, Zhu Pingping, Xiong Xifeng, Yu Chaosheng, Li Aiguo, Liu Zhihe
Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Jinan University Guangzhou 510220, Guangdong, China.
Burn and Plastic Surgery, Guangzhou Red Cross Hospital, Jinan University Guangzhou 510220, Guangdong, China.
Am J Transl Res. 2021 Sep 15;13(9):10908-10921. eCollection 2021.
Osteoarthritis (OA) is common in the elderly. Baicalin (BA) is a flavonoid monomer extracted from , which has been reported to have anti-inflammatory, anti-deformation and anti-bacterial effects.
Cultures of micromass and 3D alginate beads, Alcian blue and Safranin O (SO)/fast green staining were used to investigate chondrocyte viability and extracellular matrix (ECM) synthesis in chondrocytes of all groups. The expression of SOX9, Smad3, Aggrecan (ACAN), type II collagen (Col2α), matrix metallopetidase 9 (MMP9), MMP13 and ADAMTS5 in chondrocytes of all groups were detected by western blot or qRT-PCR.
The present study demonstrates that BA neutralized the IL-1β-induced downregulation of chondrocyte viability and ECM secretion, including ACAN and Col2α. The downregulation of SOX9, and the upregulation of MMP9, MMP13 and ADAMTS5 induced by IL-1β were reversed by BA treatment. Moreover, BA increased the nuclear translocation of Smad3 and SOX9 in chondrocytes cultured by micromass and 3D alginate beads. Interestingly, Smad3 inhibitor SIS3 reversed the promoting effect of BA on chondrocyte viability, ECM secretion, SOX9 and Smad3 nuclear translocation, and the inhibiting effect of BA on MMP9 and ADAMTS5 expressions. BA treatment also attenuated the decrease of Smad3 phosphorylation, SOX9 expression and the damage of cartilage integrity in mice which were induced by destabilization of the medial meniscus (DMM).
BA promotes chondrocyte viability and the cell matrix synthesis through TGF-β/Smad3 pathway in IL-1β-treated chondrocytes and DMM treated mice. BA is a potential therapeutic target for OA.
骨关节炎（OA）在老年人中很常见。黄芩苷（BA）是从[具体来源未给出]中提取的黄酮类单体，据报道具有抗炎、抗变形和抗菌作用。
采用微团培养和3D海藻酸钠珠培养、阿尔新蓝和番红O（SO）/固绿染色来研究所有组软骨细胞的活力和细胞外基质（ECM）合成。通过蛋白质免疫印迹法或qRT-PCR检测所有组软骨细胞中SOX9、Smad3、聚集蛋白聚糖（ACAN）、II型胶原蛋白（Col2α）、基质金属蛋白酶9（MMP9）、MMP13和含血小板反应蛋白基序的解聚素样金属蛋白酶5（ADAMTS5）的表达。
本研究表明，BA可中和IL-1β诱导的软骨细胞活力和ECM分泌的下调，包括ACAN和Col2α。IL-1β诱导的SOX9下调以及MMP9、MMP13和ADAMTS5上调被BA处理逆转。此外，BA增加了微团和3D海藻酸钠珠培养的软骨细胞中Smad3和SOX9的核转位。有趣的是，Smad3抑制剂SIS3逆转了BA对软骨细胞活力、ECM分泌、SOX9和Smad3核转位的促进作用，以及BA对MMP9和ADAMTS5表达的抑制作用。BA处理还减轻了内侧半月板不稳定（DMM）诱导的小鼠中Smad3磷酸化降低、SOX9表达降低和软骨完整性损伤。
BA通过TGF-β/Smad3途径促进IL-1β处理的软骨细胞和DMM处理的小鼠中的软骨细胞活力和细胞基质合成。BA是OA的潜在治疗靶点。
