Alam Shahenvaz, Sargeant Marisa Shauna, Patel Ronak, Jayaram Prathap
Department of Orthopedics, Musculoskeletal Institute, School of Medicine, Emory University, Atlanta, GA 30329, USA.
J Clin Med. 2024 Nov 5;13(22):6641. doi: 10.3390/jcm13226641.
Rotator cuff calcific tendinopathy and arthrofibrosis of the shoulder (adhesive capsulitis) are debilitating musculoskeletal disorders that significantly impact joint function and impair quality of life. Despite its high prevalence and common clinical presentation, the metabolic mechanisms underlying these conditions characterized by pain, and reduced mobility, remain poorly understood. This review aims to elucidate the role of metabolic processes implicated in the pathogenesis of calcific tendinopathy and shoulder arthrofibrosis. We will be focusing on the mechanistic role of how these processes contribute to disease progression and can direct potential therapeutic targets. Calcific tendinopathy is marked by aberrant calcium deposition within tendons, influenced by disrupted calcium and phosphate homeostasis, and altered cellular responses. Key molecular pathways, including bone morphogenetic proteins (BMPs), Wnt signaling, and transforming growth factor-beta (TGF-β), play crucial roles in the pathophysiology of calcification, calcium imbalance, and muscle fibrosis. In contrast, shoulder arthrofibrosis involves excessive collagen deposition and fibrosis within the shoulder joint capsule, driven by metabolic dysregulation and inflammation. The TGF-β signaling pathway and inflammatory cytokines, such as interleukin-6 (IL-6), are central to the fibrotic response. A comparative analysis reveals both shared and distinct metabolic pathways between these conditions, highlighting the interplay between inflammation, cellular metabolism, extracellular matrix remodeling, calcific deposition, and calcium migration to the glenohumeral joints, resulting in adhesive capsulitis, thereby providing insights into their pathophysiology. This review discusses current therapeutic approaches and their limitations, advocating for the development of targeted therapies that address specific metabolic dysregulations. Future therapeutic strategies focus on developing targeted interventions that address the underlying metabolic dysregulation, aiming to improve patient outcomes and advance clinical management. This review offers a comprehensive overview of the metabolic mechanisms involved in calcific tendinopathy and shoulder arthrofibrosis, providing a foundation for future research and therapeutic development.
肩袖钙化性肌腱病和肩关节纤维性关节病（粘连性关节囊炎）是使人虚弱的肌肉骨骼疾病，会显著影响关节功能并损害生活质量。尽管其患病率高且临床表现常见，但这些以疼痛和活动能力下降为特征的病症的代谢机制仍知之甚少。本综述旨在阐明参与钙化性肌腱病和肩关节纤维性关节病发病机制的代谢过程的作用。我们将重点关注这些过程如何促进疾病进展以及如何指导潜在治疗靶点的机制性作用。钙化性肌腱病的特征是肌腱内异常钙沉积，受钙和磷稳态破坏以及细胞反应改变的影响。关键分子途径，包括骨形态发生蛋白（BMPs）、Wnt信号传导和转化生长因子-β（TGF-β），在钙化、钙失衡和肌肉纤维化的病理生理学中起关键作用。相比之下，肩关节纤维性关节病涉及肩关节囊内胶原蛋白过度沉积和纤维化，由代谢失调和炎症驱动。TGF-β信号通路和炎性细胞因子，如白细胞介素-6（IL-6），是纤维化反应的核心。比较分析揭示了这些病症之间共同和不同的代谢途径，突出了炎症、细胞代谢、细胞外基质重塑、钙化沉积以及钙向盂肱关节迁移之间的相互作用，导致粘连性关节囊炎，从而为其病理生理学提供了见解。本综述讨论了当前的治疗方法及其局限性，主张开发针对特定代谢失调的靶向治疗方法。未来的治疗策略侧重于开发针对潜在代谢失调的靶向干预措施，旨在改善患者预后并推进临床管理。本综述全面概述了钙化性肌腱病和肩关节纤维性关节病所涉及的代谢机制，为未来的研究和治疗开发奠定了基础。
