MMP9 polymorphism is associated with susceptibility to non-traumatic osteonecrosis of femoral head in a Chinese Han population

Abstract

Non-traumatic osteonecrosis of femoral head (ONFH) is an orthopedic refractory disease with escalating morbidity in Chinese Han population. In our case-control study, we examined eight previously identified MMP9 single-nucleotide polymorphisms (SNPs) in 585 non-traumatic ONFH patients and 507 healthy individuals from northern China to determine whether these SNPs associated with the risk of developing non-traumatic ONFH. Genetic model and haplotype analyses were used to evaluate the association between SNPs and non-traumatic ONFH. MMP9 rs2274755 (OR, 0.740; 95% CI, 0.578-0.949; p = 0.017) was associated with a reduced risk of non-traumatic ONFH. After adjusting for age and gender, the logistic regression results showed that rs2274755 associated with a lower risk of non-traumatic ONFH in the dominant (OR=0.71, 95% CI: 0.54-0.94, p=0.016), overdominant (OR=0.73, 95% CI: 0.55-0.96, p=0.026) and log-additive (OR=0.74740; 95% CI, 0.578-0.949; p=0.017) models. In addition, the "TGC" haplotype of rs2274755 was associated with a 0.79-fold decrease in risk while the "CTC" haplotype associated with a 0.65-fold decrease risk of the non-traumatic ONFH. These results provide evidence that the MMP9 SNP at the rs2274755 locus is associated with a decreased risk of non-traumatic ONFH in a Chinese Han population.

Drug discovery in Rheumatoid Arthritis-induced Osteonecrosis of the Femoral Head

“…HGF interacts to the unique receptor c-Met to activate the PI3K-Akt signaling pathway [31,32], and MMP-9 production is induced by the receptor activator of NF-B ligand (RANKL), a constituent of the membrane-associated TNF ligand family. Both of these factors stimulate osteoclast generation and lead to pathological bone loss in RA [27], which is one of the factors leading to ONFH [33].It was discovered that blocking the PI3K-Akt pathway can also reduce the expression of MMP9 in RA mice and alleviate joint injury [34,35], which could potentially serve as a therapeutic target for RA-induced ONFH. Furthermore, HGF-transgenic mesenchymal stem cells can improve ONFH recovery and may be a promising drug for ONFH therapy [36].…”

MicroRNA‑141 inhibits the differentiation of bone marrow‑derived mesenchymal stem cells in steroid‑induced osteonecrosis via E2F3

“…It has been found that steroid-induced avascular necrosis of the femoral head is the most common type of non-traumatic osteonecrosis of the femoral head ( 3 ). It is estimated that 75,000-150,000 new cases of ONFH are diagnosed every year in China ( 4 ). Reduced bone mass and trabecular fracture may occur after the third stage of ONFH as a result of cell death in the femoral head ( 5 ).…”