Chondromodulin-1 in health, osteoarthritis, cancer, and heart disease

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.

Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs

“…Subclusters C5 and C6 preferentially expressed PRG4 and CNMD, suggesting that they may play a protective role and stabilize the chondrocyte phenotype. 49,50 To better understand the specific characteristics of IVD chondrocytes, we compared the transcriptomic differences between these chondrocyte subclusters and articular cartilage chondrocytes at different stages of osteoarthritis (stages 0-4) i The number of expressed genes associated with six matrisome patterns in each chondrocyte subcluster. ECM extracellular matrix.…”

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

“…PC1 of young discs identified known chondrocyte markers, CLEC3A ( Lau et al, 2018 ) and LECT1/2 ( Zhu et al, 2019 ), hedgehog signalling proteins, HHIPL2, HHIP, and SCUBE1 ( Johnson et al, 2012 ), and xylosyltransferase-1 (XYLT1), a key enzyme for initiating the attachment of glycosaminoglycan side chains to proteoglycan core proteins ( Silagi et al, 2018 ; Figure 2E ). Most of the proteins that were positively correlated in PC1 were coagulation factors or coagulation related, suggesting enhanced blood infiltration in aged discs.…”

SETD7 mediates the vascular invasion in articular cartilage and chondrocytes apoptosis in osteoarthriis

“…Although chondrocytes in normal joints produce antiangiogenic factors, such as chondromodulin 33 and endostatin, 34 cartilage from patients with OA lose the ability to remain avascular 35 . The expression of chondromodulin has been found decreased in OA models, especially in the area of CD31 positive staining 36 .…”