Huang Junchao, Bu Ziheng, Liu Wei, Zhou Zheng, Hu Jianhai, Yu Jianing, Wang Huajun, Xu Sudan, Wu Peng
Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Department of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Jinan University, Guangzhou 510630, China.
Mater Today Bio. 2024 Jun 15;27:101124. doi: 10.1016/j.mtbio.2024.101124. eCollection 2024 Aug.
Osteoarthritis (OA) is a prevalent chronic disease, characterized by chronic inflammation and cartilage degradation. This study aims to deepen the understanding of OA's pathophysiology and to develop novel therapeutic strategies. Our study underscores the pivotal role of Epiphycan (EPYC) and the IL-17 signaling pathway in OA. EPYC, an essential extracellular matrix constituent, has been found to exhibit a positive correlation with the severity of OA. We have discovered that EPYC modulates the activation of the IL-17 signaling pathway within chondrocytes by regulating the interaction between IL-17A and its receptor, IL-17RA. This regulatory mechanism underscores the intricate interplay between the extracellular matrix and immune signaling in the pathogenesis of OA Another finding of our study is the therapeutic effectiveness of protocatechualdehyde (PAH) in OA. PAH significantly reduces chondrocyte hypertrophy and supports cartilage tissue recovery.by targets EPYC. To reduce the side effects of orally administered PAH and maintain its effective drug concentration, we have developed a decellularized matrix hydrogel loaded with PAH for intra-articular injection. This novel drug delivery system is advantageous in minimizing drug-related side effects and ensuring sustained release PAH within the joint cavity.
骨关节炎（OA）是一种常见的慢性疾病，其特征为慢性炎症和软骨降解。本研究旨在加深对OA病理生理学的理解，并开发新的治疗策略。我们的研究强调了Epiphycan（EPYC）和IL-17信号通路在OA中的关键作用。EPYC是一种重要的细胞外基质成分，已发现其与OA的严重程度呈正相关。我们发现，EPYC通过调节IL-17A与其受体IL-17RA之间的相互作用，来调节软骨细胞内IL-17信号通路的激活。这种调节机制强调了细胞外基质与免疫信号在OA发病机制中的复杂相互作用。我们研究的另一个发现是原儿茶醛（PAH）在OA中的治疗效果。PAH通过作用于EPYC，显著减少软骨细胞肥大，并促进软骨组织恢复。为了减少口服PAH的副作用并维持其有效药物浓度，我们开发了一种负载PAH的脱细胞基质水凝胶用于关节内注射。这种新型药物递送系统有利于将药物相关副作用降至最低，并确保PAH在关节腔内持续释放。
