Hyaluronan in articular cartilage: Analysis of hip osteoarthritis and osteonecrosis of femoral head

Abstract

Hyaluronan (HA) plays crucial roles in the maintenance of high-quality cartilage extracellular matrix. Several studies have reported the HA in synovial fluid in patients with osteoarthritis (OA), but few have described the changes of HA in articular cartilage of OA or idiopathic osteonecrosis of the femoral head (ONFH). KIAA1199 was recently reported to have strong hyaluronidase activity. The aim of this study was to clarify the HA metabolism in OA and ONFH, particularly the involvement of KIAA1199. Immunohistochemical analysis of KIAA1199 and HA deposition was performed for human OA (n = 10), ONFH (n = 10), and control cartilage (n = 7). The concentration and molecular weight (MW) of HA were determined by competitive HA ELISA and Chromatography, respectively. Regarding HA metabolism-related molecules, HAS1, HAS2, HAS3, HYAL1, HYAL2, and KIAA1199 gene expression was assessed by reverse transcriptase polymerase chain reaction. Histological analysis showed the overexpression of KIAA1199 in OA cartilage, which was accompanied by decreased hyaluronic acid binding protein (HABP) staining compared with ONFH and control. Little KIAA1199 expression was observed in cartilage at the collapsed area of ONFH, which was accompanied by a slight decrease in HABP staining. The messenger RNA (mRNA) expression of HAS2 and KIAA1199 was upregulated in OA cartilage, while the mRNA expression of genes related to HA catabolism in ONFH cartilage showed mostly a downward trend. The MW of HA in OA cartilage increased while that in ONFH cartilage decreased. HA metabolism in ONFH is suggested to be generally indolent, and is activated in OA including high expression of KIAA1199. Interestingly, MW of HA in OA cartilage was not reduced.

Evaluating the Morphology of Unique Superficial Fissured Cartilage Lesions at the Femoral Head-Neck Junction in Patients with Femoroacetabular Impingement Syndrome

“…In this study, a total of 9 analytes were evaluated: matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, MMP-10, and MMP-12 (EMD Millipore, catalog No HMMP2MAG-55K-04); tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 (EMD Millipore, catalog No HTMP1MAG-54K-02); aggrecan chondroitin sulphate neopepitope CS846 (IBEX, catalog No 60-1004); and hyaluronic acid (HA; R&D systems, catalog No DHYALO). Regarding these investigated items, it has been reported that MMPs and TIMPs are involved in cartilage degeneration, 13,30 HA in cartilage is reduced by OA, 32 and CS846 is a useful diagnostic marker for early OA that has received much attention in recent years. 2,14…”

Hyaluronic Acid in Rheumatology

“…This decline in HA levels can be attributed to an imbalance between HA synthesis and degradation, with increased activity of hyaluronidases, the enzymes responsible for HA breakdown [ 71 ]. Consequently, the cartilage becomes vulnerable to wear and tear, resulting in pain, stiffness, and functional impairment [ 72 ]. Dysregulated HA metabolism, including increased synthesis and degradation, contributes to cartilage degradation, synovitis, and pain in OA [ 73 ].…”