The pericellular hyaluronan of articular chondrocytes

Abstract

The story of hyaluronan in articular cartilage, pericellular hyaluronan in particular, essentially is also the story of aggrecan. Without properly tethered aggrecan, the load bearing function of cartilage is compromised. The anchorage of aggrecan to the cell surface only occurs due to the binding of aggrecan to hyaluronan-with hyaluronan tethered either to a hyaluronan synthase or by multivalent binding to CD44. In this review, details of hyaluronan synthesis are discussed including how HAS2 production of hyaluronan is necessary for normal chondrocyte development and matrix assembly, how an abundance or deficit of pericellular hyaluronan alters chondrocyte metabolism, and whether hyaluronan size matters or changes with aging or disease. The biomechanical role and matrix assembly function of hyaluronan in addition to the functions of hyaluronidases are discussed. The turnover of hyaluronan is considered including mechanisms by which its turnover, at least in part, is mediated by endocytosis by chondrocytes and regulated by aggrecan degradation. Differences between turnover and clearance of newly synthesized hyaluronan and aggrecan versus the half-life of hyaluronan remaining within the inter-territorial matrix of cartilage are discussed. The release of neutral pH-acting hyaluronidase activity remains one unanswered question concerning the loss of cartilage hyaluronan in osteoarthritis. Signaling events driven by changes in hyaluronan-chondrocyte interactions may involve a chaperone function of CD44 with other receptors/cofactors as well as the changes in hyaluronan production functioning as a metabolic rheostat.

Melanocyte Hyaluronan Coat Fragmentation Enhances the UVB-Induced TLR-4 Receptor Signaling and Expression of Proinflammatory Mediators IL6, IL8, CXCL1, and CXCL10 via NF-κB Activation

“…The hyaluronan receptor CD44 (Aruffo et al, 1990) binds and organizes pericellular hyaluronan and governs multiple functions at the cell surface (Jokela et al, 2015;Knudson et al, 2018;Pasonen-Seppänen et al, 2012a). CD44 silencing, like HAS2 repression, partially prevented the induction of the inflammatory mediators in melanocytes after UVB, suggesting that hyaluronan-CD44 interaction was involved in the UVB response.…”

Changes in stiffness and biochemical composition of the pericellular matrix as a function of spatial chondrocyte organisation in osteoarthritic cartilage

“…It encompasses the chondrocytes, thus forming the structural, functional, and metabolic unit of articular cartilage termed the "chondron" 12 . Other key components of the PCM are the heparin-sulphate proteoglycan perlecan 13 , aggrecan monomers 14 and aggregates 15 , laminin 16 , fibronectin 17 , hyaluronan 18 , biglycan 19 , and collagen type IX 20 . The PCM acts as a mechano-sensitive cell matrix interface, protects the chondrocytes from apoptosis, and modulates biosynthetic response 21e23 .…”

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures

“…Other families of the matrix degrading enzymes can destroy the cartilage specific proteoglycans, ADAMTS4 and ADAMTS5 are described as major aggrecanases of osteoarthritis [14]. Hyaluronidases degrade hyaluronic acid, which ultimately leadsto the disintegration of the aggrecan–hyaluronan network in the cartilage matrix [15]. Four cartilage-specific hyaluronidases have been identified in the last decade [2].…”