Hendy Benjamin A, Fertala Jolanta, Nicholson Thema, Abboud Joseph A, Namdari Surena, Fertala Andrzej
Department of Orthopaedic Surgery, Sidney Kimmel Medical College Thomas Jefferson University Philadelphia Pennsylvania USA.
Rothman Institute of Orthopaedics, Shoulder and Elbow Service Thomas Jefferson University Hospital Philadelphia Pennsylvania USA.
Health Sci Rep. 2023 Feb 16;6(2):e1100. doi: 10.1002/hsr2.1100. eCollection 2023 Feb.
Arthrofibrosis is a severe scarring condition characterized by joint stiffness and pain. Fundamental to developing arthrofibrotic scars is the accelerated production of procollagen I, a precursor of collagen I molecules that form fibrotic deposits in affected joints. The procollagen I production mechanism comprises numerous elements, including enzymes, protein chaperones, and growth factors. This study aimed to elucidate the differences in the production of vital elements of this mechanism in surgical patients who developed significant posttraumatic arthrofibrosis and those who did not.
We studied a group of patients who underwent shoulder arthroscopic repair of the rotator cuff. Utilizing fibroblasts isolated from the patients' rotator intervals, we analyzed their responses to profibrotic stimulation with transforming growth factor β1 (TGFβ1). We compared TGFβ1-dependent changes in the production of procollagen I. We studied auxiliary proteins, prolyl 4-hydroxylase (P4H), and heat shock protein 47 (HSP47), that control procollagen stability and folding. A group of other proteins involved in excessive scar formation, including connective tissue growth factor (CTGF), α smooth muscle actin (αSMA), and fibronectin, was also analyzed.
We observed robust TGFβ1-dependent increases in the production of CTGF, HSP47, αSMA, procollagen I, and fibronectin in fibroblasts from both groups of patients. In contrast, TGFβ1-dependent P4H production increased only in the stiff-shoulder-derived fibroblasts.
Results suggest P4H may serve as an element of a mechanism that modulates the fibrotic response after rotator cuff injury.
关节纤维化是一种严重的瘢痕形成病症，其特征为关节僵硬和疼痛。关节纤维化瘢痕形成的根本原因是I型前胶原的加速产生，I型前胶原是I型胶原分子的前体，在受影响的关节中形成纤维化沉积物。I型前胶原的产生机制包含众多要素，包括酶、蛋白质伴侣和生长因子。本研究旨在阐明在发生显著创伤后关节纤维化的手术患者与未发生该病症的患者中，此机制关键要素产生情况的差异。
我们研究了一组接受肩袖关节镜修复术的患者。利用从患者肩袖间隙分离出的成纤维细胞，分析它们对转化生长因子β1（TGFβ1）促纤维化刺激的反应。我们比较了TGFβ1依赖的I型前胶原产生的变化。我们研究了控制前胶原稳定性和折叠的辅助蛋白脯氨酰4-羟化酶（P4H）和热休克蛋白47（HSP47）。还分析了一组参与过度瘢痕形成的其他蛋白质，包括结缔组织生长因子（CTGF）、α平滑肌肌动蛋白（αSMA）和纤连蛋白。
我们观察到两组患者的成纤维细胞中，CTGF、HSP47、αSMA、I型前胶原和纤连蛋白的产生均有显著的TGFβ1依赖的增加。相比之下，TGFβ1依赖的P4H产生仅在僵硬肩部来源的成纤维细胞中增加。
结果表明P4H可能是调节肩袖损伤后纤维化反应机制的一个要素。
