Profibrotic Behavior of Fibroblasts Derived From Patients That Develop Posttraumatic Shoulder Stiffness
BACKGROUND AND AIMS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: Results suggest P4H may serve as an element of a mechanism that modulates the fibrotic response after rotator cuff injury.
Hendy, Benjamin A.; Fertala, Jolanta; Nicholson, Thema; Abboud, Joseph A.; Namdari, Surena; and Fertala, Andrzej, "Profibrotic Behavior of Fibroblasts Derived From Patients That Develop Posttraumatic Shoulder Stiffness" (2023). Department of Orthopaedic Surgery Faculty Papers. Paper 186.
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This article is the author's final published version in Health Science Reports, Volume 6, Issue 2, Article number e1100.
The published version is available at https://doi.org/10.1002/hsr2.1100. Copyright © 2023 The Authors.