Profibrotic behavior of fibroblasts derived from patients that develop posttraumatic shoulder stiffness
Abstract 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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-02-01
|
| Series: | Health Science Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/hsr2.1100 |
| _version_ | 1797772414286823424 |
|---|---|
| author | Benjamin A. Hendy Jolanta Fertala Thema Nicholson Joseph A. Abboud Surena Namdari Andrzej Fertala |
| author_facet | Benjamin A. Hendy Jolanta Fertala Thema Nicholson Joseph A. Abboud Surena Namdari Andrzej Fertala |
| author_sort | Benjamin A. Hendy |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T21:51:27Z |
| format | Article |
| id | doaj.art-b3164917d4834750befbfc94240a23b6 |
| institution | Directory Open Access Journal |
| issn | 2398-8835 |
| language | English |
| last_indexed | 2024-03-12T21:51:27Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Health Science Reports |
| spelling | doaj.art-b3164917d4834750befbfc94240a23b62023-07-26T04:06:15ZengWileyHealth Science Reports2398-88352023-02-0162n/an/a10.1002/hsr2.1100Profibrotic behavior of fibroblasts derived from patients that develop posttraumatic shoulder stiffnessBenjamin A. Hendy0Jolanta Fertala1Thema Nicholson2Joseph A. Abboud3Surena Namdari4Andrzej Fertala5Department of Orthopaedic Surgery, Sidney Kimmel Medical College Thomas Jefferson University Philadelphia Pennsylvania USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College Thomas Jefferson University Philadelphia Pennsylvania USARothman Institute of Orthopaedics, Shoulder and Elbow Service Thomas Jefferson University Hospital Philadelphia Pennsylvania USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College Thomas Jefferson University Philadelphia Pennsylvania USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College Thomas Jefferson University Philadelphia Pennsylvania USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College Thomas Jefferson University Philadelphia Pennsylvania USAAbstract 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.https://doi.org/10.1002/hsr2.1100arthrofibrosiscollagenprofibroticscarringstiff joints |
| spellingShingle | Benjamin A. Hendy Jolanta Fertala Thema Nicholson Joseph A. Abboud Surena Namdari Andrzej Fertala Profibrotic behavior of fibroblasts derived from patients that develop posttraumatic shoulder stiffness Health Science Reports arthrofibrosis collagen profibrotic scarring stiff joints |
| title | Profibrotic behavior of fibroblasts derived from patients that develop posttraumatic shoulder stiffness |
| title_full | Profibrotic behavior of fibroblasts derived from patients that develop posttraumatic shoulder stiffness |
| title_fullStr | Profibrotic behavior of fibroblasts derived from patients that develop posttraumatic shoulder stiffness |
| title_full_unstemmed | Profibrotic behavior of fibroblasts derived from patients that develop posttraumatic shoulder stiffness |
| title_short | Profibrotic behavior of fibroblasts derived from patients that develop posttraumatic shoulder stiffness |
| title_sort | profibrotic behavior of fibroblasts derived from patients that develop posttraumatic shoulder stiffness |
| topic | arthrofibrosis collagen profibrotic scarring stiff joints |
| url | https://doi.org/10.1002/hsr2.1100 |
| work_keys_str_mv | AT benjaminahendy profibroticbehavioroffibroblastsderivedfrompatientsthatdevelopposttraumaticshoulderstiffness AT jolantafertala profibroticbehavioroffibroblastsderivedfrompatientsthatdevelopposttraumaticshoulderstiffness AT themanicholson profibroticbehavioroffibroblastsderivedfrompatientsthatdevelopposttraumaticshoulderstiffness AT josephaabboud profibroticbehavioroffibroblastsderivedfrompatientsthatdevelopposttraumaticshoulderstiffness AT surenanamdari profibroticbehavioroffibroblastsderivedfrompatientsthatdevelopposttraumaticshoulderstiffness AT andrzejfertala profibroticbehavioroffibroblastsderivedfrompatientsthatdevelopposttraumaticshoulderstiffness |