Alghamdi Ahmed, Alyami Ali H, Althaqafi Raad M M, Alzeyadi Ahmed, Alrubaei Faisal S, Alyami Almuhanad A, Singer Mohamed S, Saati Abdulelah A, Alotaibi Wasn T, Alsharif Maha O
Orthopedic Surgery, Al-Baha University, Al-Baha, SAU.
Surgery/Muscloskeletal Oncology, Limb Reconstructive Surgery, Sport Medicine and Arthroscopy, King Saud bin Abdulaziz University for Health Sciences, Jeddah, SAU.
Cureus. 2023 Mar 13;15(3):e36070. doi: 10.7759/cureus.36070. eCollection 2023 Mar.
Frozen shoulder (FS) is a common name for shoulder movement limitation with different degrees of shoulder rigidity and pain. It is characterized by varying developmental courses, different levels of shoulder movement limitation, and background ambiguity due to the multiplicity of its causative factors. Systemic inflammatory cytokines monitoring and restraining is easy to apply, fast to conduct, and needs lower costs compared to invasive methods for frozen shoulder stage evaluation and early controlling of its progress to the stage that necessitates surgical intervention. The aim of this review was to assess the recent findings concerning the role of cytokines in FS pathogenesis and the possibility of preventing or controlling their progress through targeting these cytokines by the new drugs candidates, such as hyaluronan (HA), botulinum toxin type A (BoNT A), Tetrandrine, tumor necrosis factor-stimulated gene-6 (TSG-6), and cannabidiol. Searching the PubMed site, we encountered out of 1608 records, from which 16 original studies were included for the quantitative construction of this systematic review screening of the recent studies to investigate the different FS pathogenic pathways. Most of the scenarios are centered around the inflammatory and fibrotic process triggered by synovial and capsular fibroblast stimulation. This mechanism depends mainly on alarmins cytokines, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), with the stimulation of interleukin-1 α (IL-1α), interleukin-1 β (IL-1β), tumor necrosis alpha (TNF-α), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in a joint capsule. Different pathways of transforming growth factor- β (TGF-β) stimulation, resulting in overexpression of the fibrotic factors as tenascin C (TNC), fibronectin 1, collagen I (COL 1) and collagen III (COL III), and matrix metalloproteinases (MMPs) in the capsular or synovial/capsular fibroblasts. The overall investigation of these studies led us to conclude that the new drug candidates proved their efficiency in controlling the common pathogenesis of the inflammatory and fibrotic pathways of frozen shoulder and therefore represent a prospect for easy and early controlling and efficiently treating this serious disease.
冻结肩（FS）是肩关节活动受限并伴有不同程度的肩部僵硬和疼痛的常见称谓。其特点是病程发展各异、肩关节活动受限程度不同，且由于致病因素的多样性导致病因不明。与用于冻结肩分期评估及早期控制其发展至需手术干预阶段的侵入性方法相比，监测和抑制全身炎症细胞因子操作简便、实施快速且成本较低。本综述的目的是评估有关细胞因子在冻结肩发病机制中的作用的最新研究结果，以及通过新型候选药物（如透明质酸（HA）、A型肉毒毒素（BoNT A）、粉防己碱、肿瘤坏死因子刺激基因-6（TSG-6）和大麻二酚）靶向这些细胞因子来预防或控制其进展的可能性。在PubMed网站上搜索时，我们从1608条记录中筛选出16项原始研究，用于定量构建本系统综述，以筛选近期研究来探究冻结肩不同的致病途径。大多数情况围绕滑膜和关节囊成纤维细胞刺激引发的炎症和纤维化过程。该机制主要依赖于警报素细胞因子，包括胸腺基质淋巴细胞生成素（TSLP）、白细胞介素-33（IL-33）和白细胞介素-25（IL-25），同时伴有关节囊中白细胞介素-1α（IL-1α）、白细胞介素-1β（IL-1β）、肿瘤坏死因子α（TNF-α）、环氧化酶-1（COX-1）和环氧化酶-2（COX-2）的刺激。转化生长因子-β（TGF-β）刺激的不同途径导致关节囊或滑膜/关节囊成纤维细胞中纤维化因子如腱生蛋白C（TNC）、纤连蛋白1、胶原蛋白I（COL 1）和胶原蛋白III（COL III）以及基质金属蛋白酶（MMPs）的过度表达。对这些研究的全面调查使我们得出结论，新型候选药物已证明其在控制冻结肩炎症和纤维化途径的共同发病机制方面的有效性，因此为轻松、早期控制和有效治疗这种严重疾病带来了希望。
