In the present study, we investigated the relationship between β-catenin levels and disease process in patients with ONFH. We found that in both protein level and plasma level, β-catenin was significantly higher in the ONFH group, especially in the post-collapse patients than that in control group, and it was positively associated with ARCO stages, but not with etiology. To the best of our knowledge, this is the first study effectively explain the correlation between β-catenin level and the disease severity of ONFH. Our finding suggests that β-catenin could possibly be used as a biomarker to assess the progress of ONFH.
Wnt/β-catenin signaling pathway which regulate the differentiation of bone marrow mesenchymal stem cells is closely related to the regulation of bone balance . β-catenin mainly exists in the cytoplasm, but few of them also exists in the cell membrane and the nucleus. And as the core targe and important regulator, it plays a crucial role in Wnt/β-catenin pathway. In the normal Wnt/β-catenin signaling pathway, β-catenin will pass from the cytoplasm into the nucleus for promoting the proliferation and differentiation of osteoblast, and keeping bone balance. On the contrary, when Wnt signaling pathways was suppressed, β-catenin will be degraded in the cytoplasm, thus weakening the proliferation and differentiation of osteoblast, causing a decline in bone mass. However, many studies in recent years have shown that Wnt/β-catenin signaling pathway has different effects on osteoblasts of different differentiation stages, and it needs precise regulation to maintain bone balance[17, 18]. At present, numerous studies indicated that ONFH is related to osteocyte apoptosis and bone remodeling, with increased osteocyte apoptosis and bone resorption in the necrotic area of the femoral head, but increased osteoblast activity in the sclerotic area around the necrotic area[19-21], these results were consisted with the phenomenon we found in the present study. According to the results of immunohistochemistry and plasma, our research also showed that the expression of β-catenin in ONFH patients was higher than that in normal control group, and it was positively associated with ARCO stages. At the early stage of ONFH, corresponding to ARCO Ⅰ, bone cell apoptosis was the main manifestation of femoral head lesions. Therefore, the expression of β-catenin might be decreased. Due to most patients at the early stage of ONFH were asymptomatic and very rare in clinical, they were not enrolled in our research., we will further study this problem. However, sclerosis rim can be found in X-ray film at the stage of ARCO II, which mean the osteoblast activity was enhanced. Thus, in theory, as the disease progresses, the osteoblast activity increases and so does the expression level of β-catenin. Although some animal experiments have shown that the expression of β-catenin in rats with femoral head necrosis was decreased[22-24], but this was not contradictory, because these animal experiments were only reflect the situation of early stage of ONFH.
In addition, the results from X-ray film, view of femoral head section and HE staining together showed that the pathological features of ONFH are apoptosis of osteocytes and rising number of lacunae. The ratio of lacunae was increased as the disease proceeded, which confirmed that the samples collected were trustworthy and can prove the pathological alterations in different stages. Although the exact mechanisms of ONFH are now still in dispute, but the femoral head cartilage damage caused by osteocyte apoptosis is seen highly associated with osteonecrosis.
There are certain limitations in this study. First, we have not evaluated the levels of β-catenin in stage I, which makes it difficult to calculate the early stage of ONFH. Second, a relatively small sample has limited the accuracy of the research. Even with these limitations, our study first demonstrated that β-catenin could possibly be used as a signal of disease progression in ONFH.