Murphy Lance A, Scanzello Carla R
Perelman School of Medicine, University of Pennsylvania MSTP, Philadelphia, PA, USA.
VA RRDT Cartilage Regeneration with Advanced Technologies to Enable Motion (CReATE Motion) Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Connect Tissue Res. 2025 Aug 13:1-7. doi: 10.1080/03008207.2025.2540950.
Osteoarthritis (OA) is the most common musculoskeletal-related disease affecting over 27 million US adults, and no disease-modifying agents are currently available. Signs of bone remodeling are a major hallmark of OA, and include subchondral sclerosis (seen on x-ray), subchondral bone marrow lesions (seen on MRI), and osteophytosis. Recent work suggests subchondral bone remodeling is likely a driver of pain in OA. In this review, we seek to provide an overview on what is known about the cellular and molecular mechanisms that play a role in osteoarthritic subchondral bone remodeling and associated pain. Searching for "subchondral bone remodeling" "pain" and "osteoarthritis," we reviewed publications from 2015 onward. We found new details of how osteoblasts, osteoclasts, and osteocytes communicate in both autocrine and paracrine manners in OA, allowing identification of potential candidates that play a role in the aberrant bone remodeling seen in OA. Furthermore, there is new knowledge regarding mechanisms of how bone cells communicate with nociceptive neurons, providing potential candidates to target for treatment of OA pain. Recent clinical trials targeting OA-associated bone remodeling have been published with some encouraging results. In the future, more work is necessary to understand the inciting events that lead to the pathogenic cell behaviors, and unravel the complex cellular communication detailed in this review. In addition, efforts to understand the discordant results from recent trials of existing agents targeting bone remodeling and to develop novel bone-targeted agents for OA are needed.
骨关节炎（OA）是最常见的肌肉骨骼相关疾病，影响着超过2700万美国成年人，目前尚无改善病情的药物。骨重塑迹象是OA的主要标志，包括软骨下硬化（X线可见）、软骨下骨髓损伤（MRI可见）和骨赘形成。最近的研究表明，软骨下骨重塑可能是OA疼痛的驱动因素。在本综述中，我们旨在概述目前已知的在骨关节炎软骨下骨重塑及相关疼痛中起作用的细胞和分子机制。通过搜索“软骨下骨重塑”“疼痛”和“骨关节炎”，我们回顾了2015年以来的出版物。我们发现了成骨细胞、破骨细胞和骨细胞在OA中以自分泌和旁分泌方式相互通讯的新细节，从而确定了在OA异常骨重塑中起作用的潜在候选因素。此外，关于骨细胞与伤害性神经元通讯机制有了新的认识，为OA疼痛治疗提供了潜在的靶点。最近针对OA相关骨重塑的临床试验已经发表，取得了一些令人鼓舞的结果。未来，有必要开展更多工作来了解导致致病细胞行为的起始事件，并阐明本综述中详细介绍的复杂细胞通讯。此外，还需要努力理解现有针对骨重塑药物近期试验结果不一致的原因，并开发针对OA的新型骨靶向药物。
