FGF23 and SOX9 expression in haemophilic cartilage: In vitro studies of the effects of iron

Abstract

Introduction Clarifying the links between iron and FGF23, SOX9 expression in chondrocytes would be helpful for comprehending articular cartilage degradation pathogenesis in blood‐induced arthritis and exploring new protective methods. Aim The purpose of this study was to determine iron regulation of fibroblast growth factor 23 (FGF23) and SRY‐box 9 (SOX9) in human chondrocytes, an area which is unexplored in blood‐induced arthritis cartilage degradation pathogenesis. Methods Expression of FGF23, SOX9, MMP13 and collagen Ⅱ in articular cartilage of patients with osteoarthritis (OA) or haemophilic arthritis (HA) was determined by western blot (WB). Iron‐induced FGF23 and SOX9 mRNA and protein expression in primary human normal chondrocyte cells (HUM‐iCell‐s018) was quantified by qRT‐PCR and WB, respectively. Results We found that compared with OA patients, the expression of FGF23, MMP13 in articular cartilage of patients with HA was up‐regulated, while the expression of SOX9, collagen Ⅱ was down‐regulated. Iron‐induced FGF23 and suppressed SOX9 expression in chondrocytes in a dose‐dependent manner. Conclusions These findings demonstrated that iron was involved in hemophilic cartilage lesion directly via changing cartilage phenotype through regulation of FGF23 and SOX9 expression in chondrocytes.

Hemophilic Arthropathy: Barriers to Early Diagnosis and Management

“…9 These inflammatory changes contribute to cartilage damage through the production of tissue-destroying enzymes and cytokines 10 leading to joint destruction. A recent study by Zheng et al 11 has shown how iron is involved in cartilage injury through regulation of FGF23 and SOX9 expression in chondrocytes in patients with hemophilia who have developed hemarthrosis. A high level of COL-18N has been noted in patients with hemophilia A 12 , which could be used as a potential marker to monitor the development of arthropathy, making it possible to adapt the best treatment to prevent further joint damage.…”

Towards Personalized Treatment in Haemophilia: The Role of Genetic Factors in Iron and Heme Control to Identify Patients at Risk for Haemophilic Arthropathy

“…Moreover, iron catalyzes the conversion of hydrogen peroxide, produced by activated chondrocytes, into hydroxyl radicals, leading to chondrocyte apoptosis [12]. Iron affects fibroblast growth factor 23 and SRY-box 9 expression, causing cartilage degeneration in HA [18]. Also, subchondral bleeding is suggested to contribute to HA development by affecting subchondral bone health and probably inducing subchondral cyst formation [19].…”

Foam roller-based self-induced myofascial therapy in patients with hemophilic knee arthropathy: a multicenter, single-blind, randomized clinical study

“…These inflammatory changes contribute to cartilage damage, through the production of enzymes and cytokines that destroy the tissue, leading to joint destruction. 6 A recent study 7 has shown how iron is involved in cartilage injury through the regulation of the expression of FGF23 and SOX9 in chondrocytes in patients with hemophilia who have developed hemarthrosis. A high level of COL-18N has been observed in patients with hemophilia A, and it can be used as a potential marker to monitor the development of arthropathy, allowing the best treatment to be adapted to prevent further joint damage.…”