PTP1B as a novel therapeutic target in frozen shoulder: evidence from human capsular tissue analysis

Frozen shoulder (FS) is a common fibroinflammatory disorder of the glenohumeral joint capsule, characterized by persistent pain and progressive restriction of range of motion. The fibroblast-to-myofibroblast transition is a central pathological event driving capsular fibrosis, yet the molecular regulators underlying this process remain poorly defined. Protein tyrosine phosphatase 1B (PTP1B) has emerged as a key regulator of fibrosis in multiple organs, but its role in musculoskeletal fibrosis, particularly in FS, has not been investigated.

In this prospective case-control study, glenohumeral capsular tissues were collected from 21 patients with idiopathic FS and 21 matched controls with rotator cuff tears during arthroscopic surgery. Tissue samples were evaluated using histology, immunofluorescence, and Western blotting. Clinical function was assessed preoperatively using the American Shoulder and Elbow Surgeons and Constant-Murley scores.

FS patients exhibited significantly worse functional outcomes across all domains, including pain, range of motion, and activities of daily living. Histopathological analysis revealed pronounced fibroblast proliferation, dense collagen deposition, hypervascularity, and perivascular adipocyte accumulation in FS capsules compared to controls. Critically, PTP1B expression was significantly upregulated in FS tissues. PTP1B immunoreactivity was prominently localized to α-SMA⁺ myofibroblasts. Co-localization studies confirmed an enrichment of PTP1B within activated myofibroblasts, indicating its specific involvement in fibrotic transdifferentiation.

This study identified PTP1B as a novel biomarker that was upregulated in FS and was specifically associated with myofibroblast activation and capsular fibrosis. These findings position PTP1B as a promising therapeutic target for mitigating fibrosis and functional impairment in FS.