| Objective:The purpose of this study is to analyze the morphological changes in subchondral bone tissue of patients with hemophilic arthritis(HA),and compare them with those of patients with osteoarthritis(OA).We aim to describe the phenomenon of iron deposition in the subchondral bone of HA,and explore the effects of iron overload on the bone destruction in HA subchondral bone and the expression of ferroptosis related proteins in HA subchondral bone.The ultimate goal is to provide guidance for the prevention and treatment of subchondral bone injury in patients with hemophilic arthritis.Method:Ten male patients who underwent primary total knee replacement surgery due to hemophilic arthritis(HA)and ten male patients who underwent primary total knee replacement surgery due to osteoarthritis(OA)were selected.The bone tissue of the tibial plateau that was removed during surgery was obtained from both groups,and micro-CT scanning was used to analyze the morphological parameters of the subchondral bone in both groups.HE and TRAP staining were used to observe changes in the subchondral bone plate and trabecular structure as well as morphological characteristics.Prussian blue(Perls)staining was used to evaluate iron deposition in the subchondral bone,and tissue iron content was measured.Finally,Western Blot(WB)was used to detect the expression levels of GPX4,SLC7A11,ACSL4,and P53ferroptosis related proteins in both groups of specimens.Results:The results of micro-CT scanning showed that the Tb.Sp of HA group was higher than that of OA group(P<0.001)in both inner and outer sides;the Bv/Tv,Con.D,BMD,Tb.Th,and Tb.N of HA group were all lower than those of OA group(P<0.001),indicating that the degree of bone destruction in the subchondral bone of HA group was more severe and the trabeculae were more sparse.The Tb.Sp of HA and OA groups on the inner and outer sides was lower than that on the outer side(P<0.001),while the Bv/Tv,Tb.Th,and Con.D were higher than those on the outer side(P<0.001).The BMD of HA group on the inner and outer sides was lower than that of OA group(P<0.001),but there was no significant difference in the BMD between the two groups on the inner and outer sides(P=0.851).HE staining results showed that the subchondral bone plate on the inner and outer sides of HA and OA groups was thicker than that on the outer side(P<0.001),and the trabeculae in the subchondral bone were sparser than those on the outer side.The subchondral bone plate on the inner and outer sides of HA group was thicker than that of OA group(P<0.001),while the trabeculae were sparser than those of OA group.TRAP staining results showed that the number of TRAP~+osteoclasts in the subchondral bone of HA group was significantly higher than that of OA group(P<0.001),and the defects and damage of trabeculae were obvious at the site where TRAP~+osteoclasts gathered.Perls staining results showed that there was a more obvious iron deposition phenomenon around the subchondral bone in HA group,while there was also iron deposition in the subchondral bone of OA group but less obvious than that of HA group.The detection of tissue iron content showed that the tissue iron content of HA group was significantly higher than that of OA group(P<0.001).Western blotting results showed that compared with OA group,the expression levels of ACSL4 and P53 proteins in HA group were increased,while the expression levels of GPX4 and SLC7A11 proteins were decreased(P<0.001),which not only confirmed the phenomenon of ferroptosis in the subchondral bone tissues of both HA and OA,but also showed a more obvious trend of ferroptosis in HA group.Conclusions:Compared with OA patients,HA subchondral bone tissue has higher iron content,more severe bone destruction,and a more obvious trend of ferroptosis,indicating that subchondral bone destruction in HA may be related to iron overload.Therefore,intervention in the iron metabolism process of HA may help to intervene in the progression of HA. |
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