Abstract
The human chondromodulin-1 (Chm-1, Chm-I, CNMD, or Lect1) gene encodes a 334 amino acid type II transmembrane glycoprotein protein with characteristics of a furin cleavage site and a putative glycosylation site. Chm-1 is expressed most predominantly in healthy and developing avascular cartilage, and healthy cardiac valves. Chm-1 plays a vital role during endochondral ossification by the regulation of angiogenesis. The anti-angiogenic and chondrogenic properties of Chm-1 are attributed to its role in tissue development, homeostasis, repair and regeneration, and disease prevention. Chm-1 promotes chondrocyte differentiation, and is regulated by versatile transcription factors, such as Sox9, Sp3, YY1, p300, Pax1, and Nkx3.2. Decreased expression of Chm-1 is implicated in the onset and progression of osteoarthritis and infective endocarditis. Chm-1 appears to attenuate osteoarthritis progression by inhibiting catabolic activity, and to mediate anti-inflammatory effects. In this review, we present the molecular structure and expression profiling of Chm-1. In addition, we bring a summary to the potential role of Chm-1 in cartilage development and homeostasis, osteoarthritis onset and progression, and to the pathogenic role of Chm-1 in infective endocarditis and cancers. To date, knowledge of the Chm-1 receptor, cellular signalling, and the molecular mechanisms of Chm-1 is rudimentary. Advancing our understanding the role of Chm-1 and its mechanisms of action will pave the way for the development of Chm-1 as a therapeutic target for the treatment of diseases, such as osteoarthritis, infective endocarditis, and cancer, and for potential tissue regenerative bioengineering applications.