Signaling pathway networks in frozen shoulder fibrosis: from inflammatory initiation to fibrotic progression

Frozen shoulder, also known as adhesive capsulitis, is characterized by fibrosis, thickening, and contracture of the shoulder joint capsule. Through a systematic review of existing research, we have analyzed the complex molecular network of shoulder fibrosis. Previous studies have found that the disease begins with inflammation of the nuclear factor kappa B (NF-κB) and leptin/Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathways, and the transforming growth factor-beta (TGF-β) pathway is the key cause of fibrosis. Wingless/Int (WNT) and potentially Hippo pathways may contribute to fibrotic progression. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt), mitogen-activated protein kinase (MAPK), and hypoxia-inducible factor (HIF-1) pathways are also related to abnormal cell proliferation, inflammatory response, and hypoxia adaptation, respectively. Technologies such as single-cell sequencing also show the heterogeneity of fibroblasts and their role in pathological networks. We point out the current limitations of pathway interaction research and look forward to the future use of multi-omics and spatial technology to gain an in-depth understanding of the mechanism and provide a theoretical basis for the formulation of treatment strategies for key nodes.