Osteoarthritis (OA) is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the body. The molecular mechanisms of OA are currently unknown. OA is a heterogeneous disease that affects the entire joint, and multiple tissues are altered during OA development. To better understand the pathological mechanisms of OA, new approaches, methods, and techniques need to be used to understand OA pathogenesis. In this review, we first focus on the epigenetic regulation of OA, with a particular focus on DNA methylation, histone modification, and microRNA regulation, followed by a summary of several key mediators in OA-associated pain. We then introduce several innovative techniques that have been and will continue to be used in the fields of OA and OA-associated pain, such as CRISPR, scRNA sequencing, and lineage tracing. Next, we discuss the timely updates concerning cell death regulation in OA pathology, including pyroptosis, ferroptosis, and autophagy, as well as their individual roles in OA and potential molecular targets in treating OA. Finally, our review highlights new directions on the role of the synovial lymphatic system in OA. An improved understanding of OA pathogenesis will aid in the development of more specific and effective therapeutic interventions for OA.

骨关节炎 (OA) 是最常见的退行性关节疾病，会导致身体关节疼痛肿胀和永久性损伤。OA 的分子机制目前尚不清楚。骨关节炎是一种影响整个关节的异质性疾病，在骨关节炎的发展过程中，多个组织都会发生改变。为了更好地了解 OA 的病理机制，需要使用新的途径、方法和技术来了解 OA 的发病机制。在这篇综述中，我们首先关注 OA 的表观遗传调控，特别关注 DNA 甲基化、组蛋白修饰和 microRNA 调控，然后总结 OA 相关疼痛的几个关键介质。然后我们介绍了一些已经并将继续用于 OA 和 OA 相关疼痛领域的创新技术，例如 CRISPR、scRNA 测序和谱系追踪。接下来，我们讨论 OA 病理学中细胞死亡调控的最新进展，包括细胞焦亡、铁死亡和自噬，以及它们在 OA 中的各自作用以及治疗 OA 的潜在分子靶点。最后，我们的综述强调了滑膜淋巴系统在 OA 中的作用的新方向。加深对 OA 发病机制的了解将有助于制定更具体、更有效的 OA 治疗干预措施。