Collagen I: a kingpin for rotator cuff tendon pathology.

Derangements in tendon matrisome are pathognomonic for musculoskeletal disorders including rotator cuff tendinopathies (RCT). Collagen type-1 accounts for more than 85% of the dry weight of tendon extracellular matrix (ECM). The understanding of basic tendon physiology, organization of ECM, structure and function of component biomolecules of matrisome and the underlying regulatory mechanisms reveal the pathological events associated with RCT. Histomorphological evidence from RCT patients and animal models illustrate that ECM disorganization is the major hallmark in tendinopathy where a significant decrease in type-1 collagen is prevalent. However, the molecular events and regulatory signals associated with the regulation of collagen organization and its composition switch in response to pathological stimuli are largely unknown. The elucidation of various regulatory signalling pathways associated with collagen type-1 gene expression could benefit to develop novel promising therapeutic approaches to restore the tendon ECM. The major focus of the article is to critically evaluate tendon architecture regarding type-1 collagen, the molecular events associated with gene expression, secretion and maturation, the possible mechanisms of type-1 collagen regulation and its translational significance in RCT management.