Versican contributes to ligament formation of knee joints

Abstract

Versican is a large proteoglycan in the extracellular matrix. During embryonic stages, it plays a crucial role in the development of cartilage, heart, and dermis. Previously, we reported thatPrx1-Vcanconditional knockout mice, lacking Vcan expression in mesenchymal condensation areas of the limb bud, show the impaired joint formation and delayed cartilage development. Here, we investigated their phenotype in adults and found that they develop swelling of the knee joint. Histologically, their newborn joint exhibited impaired formation of both anterior and posterior cruciate ligaments. Immunostaining revealed a decrease in scleraxis-positive cells in both articular cartilage and ligament ofPrx1-Vcanknee joint, spotty patterns of type I collagen, and the presence of type II collagen concomitant with the absence of versican expression. These results suggest that versican expression during the perinatal period is required for cruciate ligaments’ formation and that its depletion affects joint function in later ages.

Proteoglycan Dysfunction: A Common Link Between Intervertebral Disc Degeneration and Skeletal Dysplasia

“…Functionally, based on its structure and localization with elastin and fibulin-1, a glycoprotein that is incorporated into fibrillar ECM, versican is suggested to contribute to the organization of the disc ECM and provide structural support and resilience to mechanical forces [ 31 ]. In cartilage development, the balance of versican expression is important in mediating local transforming growth factor beta (TGF-β) in chondrocyte differentiation and digit joint formation [ 32 - 34 ]. Reductions in versican can compromise chondrogenesis and synovial joint development [ 35 ].…”

“…31 In cartilage development, the balance of versican expression is important in mediating local transforming growth factor beta (TGF-β) in chondrocyte differentiation and digit joint formation. [32][33][34] Reductions in versican can compromise chondrogenesis and synovial joint development. 35 Mutations in the human versican gene result in the (B) In healthy state, there is an abundance of large proteoglycans that maintain tissue hydration and collagen fibril integrity.…”

Versican and versikine: The dynamism of the extracellular matrix

“…59 Prx1-Vcan mice show the impaired formation of cruciate ligaments. 60 While Vcan is not essential for cartilage development, it is required for joint and ligament formation. Analysis of Prx1-Vcan mice alone does not clarify the impact of Vcan processing, which needs to be investigated.…”

“…Vcan expression remains on the surface of articular cartilage 58 and synovia 59 . Prx1‐Vcan mice show the impaired formation of cruciate ligaments 60 . While Vcan is not essential for cartilage development, it is required for joint and ligament formation.…”