Untitled

Abstract

Hyaluronan (HA), an important component of connective tissues, is highly metabolically active, but the mechanisms involved in its catabolism are still largely unknown. We hypothesized that a protein similar to sperm PH-20, the only mammalian hyaluronidase known to be active at neutral pH, could be expressed in connective tissue cells. An mRNA transcript similar to that of PH-20 was found in chondrocytes, synoviocytes, and dermal fibroblasts, and its levels were enhanced upon stimulation with IL-1. In cell layers extracted with Triton X-100 -but not with octylglucoside -and in culture media, a polyclonal antipeptide anti-PH-20 antibody identified protein bands with a molecular weight similar to that of sperm PH-20 (60 to 65 kDa) and exhibiting a hyaluronidase activity at neutral pH. Further, upon stimulation with IL-1, the amounts of the neutral-active hyaluronidase increased in both cell layers and culture media. These findings contribute potential important new insights into the biology of connective tissues. It is likely that PH-20 facilitates cell-receptor-mediated uptake of HA, while overexpression or uncontrolled expression of the enzyme can cause great havoc to connective tissues: not only does HA fragmentation compromise the structural integrity of tissues, but also the HA fragments generated are highly angiogenic and are potent inducers of proinflammatory cytokines. On the other hand, the enzyme activity may account for the progressive depletion of HA seen in osteoarthritis cartilage, a depletion that is believed to play an important role in the apparent irreversibility of this disease process.

Involvement of ADAMTS5 and hyaluronidase in aggrecan degradation and release from OSM-stimulated cartilage

“…Among the hyaluronidases reported to be expressed in cartilage, HYAL-2 and SPAM-1 (PH-20) are the primary candidates for the extracellular degradation of HA, as both enzymes are known to be active at neutral pH and are expressed at the cell surface of chondrocytes (Cherr et al ., 1996; Rai et al ., 2001; El Hajjaji et al ., 2005). However, high release and extensive HA degradation observed in the OSM cultures, suggest the presence of a hyaluronidase activity within the ECM (Durigova et al ., 2008a).…”

“…Thus, it is possible that membrane-bound HYAL-2 and/or SPAM-1 are released into the ECM through phospholipase action in the presence of OSM. In addition, it has been shown that proinflammatory cytokines such as IL-1β or TNFα can induce the gene expression and activity of both hyaluronidases in articular chondrocytes (Flannery et al ., 1998; El Hajjaji et al ., 2005). …”

Chondroitin Sulfate/Hyaluronic Acid-Blended Hydrogels Suppress Chondrocyte Inflammation under Pro-Inflammatory Conditions

“…The exception was the difference in the dry mass of the gels with the 3:7 −Col formulation, where a small but significant change in mass occurred. Under pro-inflammatory conditions, it has been demonstrated that chondrocyte hyaluronidase activity is upregulated. − In OA, this upregulation of hyaluronidase activity is responsible for the fragmentation of HA and the release of aggrecan from the cartilage. Hyaluronidase can be both cell-membrane-bound , and extracellular .…”

Investigation of dorsal/ventral skin and the parotoid region of Lyciasalamandra billae and Lyciasalamandra luschani basoglui (Urodela: Salamandridae)

“…Therefore it is used in medicine in conjunction with other drugs to speed their dispersion and delivery. Some bacteria, such as Staphylococcus aurens, Streptococcus pyogenes and Clostridium perfringens produce hyaluronidase to hydrolysis of hyaluronic acid as means of increasing mobility through the body's tissues (Ponnuraj & Jedrzejas 2000;Lin & Stern 2001;Lokeshwar et al 2002;Hajjaji et al 2005;Kim et al 2005;Girish & Kemparaju 2006;Necas et al 2008). Based on these data, HA probably acts as a chemical and biological defence barrier.…”