Perlecan Functions in Chondrogenesis: Insights from in vitro and in vivo Models

Abstract

Perlecan is a large heparan sulfate proteoglycan that is typically found in basal lamina of adult and embryonic tissues. Recent studies have demonstrated that perlecan accumulates impressively during cartilage development and is maintained as the major heparan sulfate proteoglycan of adult cartilage. In vertebrates, perlecan mutations result in skeletal defects. Moreover, in vitro studies indicate that perlecan can stimulate early stages of cartilage differentiation and cooperate with chondrogenic growth factors to promote this process. This short article will summarize these results and propose a model for perlecan function that incorporates these genetic and cell biological findings.

The CS Sulfation Motifs 4C3, 7D4, 3B3[−]; and Perlecan Identify Stem Cell Populations and Their Niches, Activated Progenitor Cells and Transitional Areas of Tissue Development in the Fetal Human Elbow

“…The presence of cells expressing the 4C3 and 7D4 CS sulfation motifs within the presumptive articular cartilage and perichondrial tissue of the fetal elbow observed in this study provides further evidence of these as developmental markers. Perlecan also has a widespread distribution in articular cartilage and promotes chondrogenesis [52][53][54][55][56]. Perlecan was found localized to the surface regions of the perichondrium in this study where it may provide a unique niche microenvironment conducive to the maintenance of progenitor cell populations underlying the fibrous perichondrium [42,43].…”

Comparative spatial and temporal localisation of perlecan, aggrecan and type I, II and IV collagen in the ovine meniscus: an ageing study

“…Perlecan also acts as a low affinity co-receptor for fibroblast growth factors (FGFs)-1, 2, 7, 9 and binds connective tissue growth factor (CTGF). The FGFs have potent cell proliferative and matrix synthesis promoting properties (Klint and Claessen-Welsh 1999;Chang et al 2000;Knox et al 2001Knox et al , 2002Hassell et al 2002); furthermore, CTGF modulates bone morphogenetic protein and transforming growth factor (TGF)-b signalling and co-ordinates chondrogenesis and angiogenesis during skeletal development (Abreu et al 2002;Ivkovic et al 2003;Nishida et al 2003;Gomes et al 2004). …”

Perlecan: how does one molecule do so many things?

“…However, to date there has been no detailed analysis of cartilage structures in these animals. Furthermore, it is possible that domain V of perlecan, which can carry HS chains under some circumstances [12,59], may compensate for the lack of domain I HS [60]. In support of this, perlecan isolated from the kidneys of these same perlecan-HS-deficient mice was recently shown to be substituted with either HS or CS [61].…”