The Structure, Location, and Function of Perlecan, a Prominent Pericellular Proteoglycan of Fetal, Postnatal, and Mature Hyaline Cartilages

Abstract

The aim of this study was to immunolocalize perlecan in human fetal, postnatal, and mature hyaline cartilages and to determine information on the structure and function of chondrocyte perlecan. Perlecan is a prominent component of human fetal (12-14 week) finger, toe, knee, and elbow cartilages; it was localized diffusely in the interterritorial extracellular matrix, densely in the pericellular matrix around chondrocytes, and to small blood vessels in the joint capsules and perichondrium. Aggrecan had a more intense distribution in the marginal regions of the joint rudiments and in para-articular structures. Perlecan also had a strong pericellular localization pattern in postnatal (2-7 month) and mature (55-64 year) femoral cartilages, whereas aggrecan had a prominent extracellular matrix distribution in these tissues. Western blotting identified multiple perlecan core protein species in extracts of the postnatal and mature cartilages, some of which were substituted with heparan sulfate and/or chondroitin sulfate and some were devoid of glycosaminoglycan substitution. Some perlecan core proteins were smaller than intact perlecan, suggesting that proteolytic processing or alternative splicing had occurred. Surface plasmon resonance and quartz crystal microbalance with dissipation experiments demonstrated that chondrocyte perlecan bound fibroblast growth factor (FGF)-1 and -9 less efficiently than endothelial cell perlecan. The latter perlecan supported the proliferation of Baf-32 cells transfected with FGFR3c equally well with FGF-1 and -9, whereas chondrocyte perlecan only supported Baf-32 cell proliferation with FGF-9. The function of perlecan therefore may not be universal but may vary with its cellular origin and presumably its structure.

Mast Cells Produce Novel Shorter Forms of Perlecan That Contain Functional Endorepellin

“…N-terminal sequencing of fragments within the 130 kDa band showed that it was a mix of peptides corresponding to sequences in domains II, III, IV, and V, suggesting the presence of the perlecan protein core. The production of perlecan with various molecular mass species similar to those described in this paper have been described previously for human (35) and bovine (35,36) cartilage extracts, but the fragments were not characterized with respect to what proteases might be responsible for the cleavage patterns demonstrated. N-terminal sequencing of the bands described here revealed many putative cleavage sites of most of the major classes of proteases, including the serine and cysteine proteases as well as the metalloproteinases.…”

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].…”

Perlecan a multifunctional extracellular proteoglycan scaffold

“…It is not clear how widespread alternative splicing is for perlecan, although this seems likely. Recent studies indicate that perlecan variants occur in cartilage although it is not clear if this results from proteolysis, alternative splicing or both (Melrose et al 2006). Moreover, mammalian mutations in Smu-1 also result in increased expression of perlecan splice variants suggesting that this process is conserved throughout evolution (Sugaya et al 2006).…”