
혈우병 환자의 관절에서 반복적인 출혈은 혈우병성 관절병증을 유발하며, 이는 연골의 심각한 손상을 특징으로 한다. 이 연구에서는 혈우병성 관절병증 연골에서 DNA 메틸화 변화와 TNXB 발현 감소가 관찰되었으며, TNXB 억제가 연골세포 세포사와 세포외기질 분해를 촉진시켜 관절 퇴행을 악화시킨다는 것을 밝혔다.


coremsg

Recurrent joint bleeding in hemophilia patients frequently causes hemophilic arthropathy (HA). Drastic degradation of cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. In HA cartilages, we found server matrix degradation and increased expression of DNA methyltransferase proteins. We thus performed genome-wide DNA methylation analysis on human HA (N = 5) and osteoarthritis (N = 5) articular cartilages, and identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses revealed the association between DMR genes (DMGs) and extracellular matrix (ECM) organization. Among these DMGs, Tenascin XB (TNXB) expression was down-regulated in human and mouse HA cartilages. The loss of Tnxb in F8-/- mouse cartilage provided a disease-promoting role in HA by augmenting cartilage degeneration and subchondral bone loss. Tnxb knockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed chondroprotective effects following Tnxb knockdown. Together, our findings indicate that exposure of cartilage to blood leads to alterations in DNA methylation, which is functionally related to ECM homeostasis, and further demonstrate a critical role of TNXB in HA cartilage degeneration by activating AKT signaling. These mechanistic insights allow development of potentially new strategies for HA cartilage protection.

### Competing Interest Statement

The authors have declared no competing interest.

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

혈우병성-관절병증에서-tnxb의-비정상적인-메틸화와-발현이-akt-신호전달을-통해-연골세포-세포사와-세포외기질-분해를-촉진시킨다


혈우병성 관절병증에서 TNXB의 비정상적인 메틸화와 발현이 AKT 신호전달을 통해 연골세포 세포사와 세포외기질 분해를 촉진시킨다
