ADAMTS‐4 as a possible distinguishing indicator between osteoarthritis and haemophilic arthropathy

Abstract

Introduction Osteoarthritis (OA) and haemophilic arthropathy (HA) are clinically similar, but pathologically distinct conditions which result in joint pain and loss of function. Distinguishing their disease mechanisms is therefore a key step in the development of curative therapy, as opposed to current symptomatic treatments. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 is a metzincin‐family member proteoglycan with known local involvement in OA pathogenesis. Aim To investigate the potential differences and discriminatory potential of ADAMTS‐4 between OA and HA patients. Methods We determined ADAMTS‐4 plasma concentrations by ELISA in patients with HA and OA. This pilot cross‐sectional study included N = 40 male participants equally divided across four subgroups: haemophilia patients with severe or mild HA and control subjects with severe or mild/no OA. Results Our study showed a striking elevation in plasma ADAMTS‐4 expression levels in HA patients as compared to OA, as well as an increase in patients with severe as compared to mild HA. By performing the binomial logistical analysis and fitting the receiver–operator curve (ROC) (cut‐off probability .5), ADAMTS‐4 had a sensitivity of 95% and specificity of 50% in discriminating between HA and OA among our study participants. Conclusion Uncovering the marked differences in plasma levels of ADAMTS‐4 in patients with HA versus OA potentially sheds new light on the mechanisms of HA pathogenesis and could foster more research into the roles ADAMTS‐4 and other matrix metalloproteinases (MMPs) play in HA versus OA.

The good, the bad and the ugly of pain in haemophilia: Recent evidence on the epidemiology, molecular mechanisms and knowledge gaps preventing optimal treatment

“…30 Repetitive intra-articular bleedings can lead to synovium hypertrophy due to blood-derived iron deposition and then to hypertrophic synovium (HS), with increased vascular perfusion and the activation of inflammatory pathways. 15,31 Once repetitive bleedings have led to HS, a vicious cycle of bleeding-synovitis-bleeding could emerge due to the profusion and fragility of vessels enriching the synovium. HS should be submitted to enhanced haematological treatment and, if not sufficient to prevent haemarthroses, HS should be corrected with arthroscopic, chemical, radioactive or open synovectomy.…”

“…This is of particular relevance as, although clinically similar, haemarthrosis and osteoarthritis show differences in their pathogenesis, and a distinction during diagnosis is relevant to the choice of an adequate therapeutic strategy. 31…”

“…Haemarthrosis, which represents the most frequent type of bleeding episodes in PWH, is a very painful event accompanied by stiffness, swelling and restricted mobility 30 . Repetitive intra‐articular bleedings can lead to synovium hypertrophy due to blood‐derived iron deposition and then to hypertrophic synovium (HS), with increased vascular perfusion and the activation of inflammatory pathways 15,31 . Once repetitive bleedings have led to HS, a vicious cycle of bleeding‐synovitis‐bleeding could emerge due to the profusion and fragility of vessels enriching the synovium.…”

“…The sense of fullness within the joint was associated with the highest risk for bleeding; in contrast, symptoms related to arthritic flare included a lack of sponginess with movement. This is of particular relevance as, although clinically similar, haemarthrosis and osteoarthritis show differences in their pathogenesis, and a distinction during diagnosis is relevant to the choice of an adequate therapeutic strategy 31 …”

Aberrant methylation and expression of TNXB promote chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling

“…Osteoarthritis (OA) is often used as “disease” control to reveal the characteristics in HA 24,25 , although the mechanistic and phenotypic are different between HA and OA. In this study, 5 HA and 5 OA knee cartilage specimens were collected from patients undergoing total knee replacement surgery.…”