A single-nucleotide polymorphism in<i>MMP9</i>is associated with decreased risk of steroid-induced osteonecrosis of the femoral head

Du, Jieli; Liu, Wanlin; Jin, Tianbo; Zhao, Zhenqun; Bai, Rui; Xue, Huiqin; Chen, Junyu; Sun, Mingqi; Zhang, Xiyang; Wang, Guoqiang; Wang, Jianzhong

doi:10.18632/oncotarget.12034

Cited by 21 publications

(16 citation statements)

References 36 publications

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“…The studies have also suggested that mechanical support and adjustment of bone cell metabolism can prevent collapse [25]. To comprehensively understand the biological behavior of osteocytes, an increasing number of studies have focused on the differential expression of miRNAs associated with osteonecrosis of the femoral head [23][24][26][27][28]. We evaluated whether the decrease in structural strength was associated with the differential expression of relevant miRNAs, which may lead to faster apoptosis and an increased imbalance with bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of miR-195-5p in collapse of steroid-induced osteonecrosis of the femoral head

Pei

et al. 2017

Oncotarget

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BackgroundFemoral head collapse is a key reference point for determining a treatment regimen of femoral head osteonecrosis. However, there are no effective preventive measures and the efficacy of hip-preserving surgery is unsatisfactory due to the unclear mechanism of collapse. This study aimed to identify and validate miRNAs differentially expressed in collapse and non-collapse areas of the osteonecrotic femoral head, and to predict the target genes and pathways of these miRNAs.ResultsNine samples passed the quality control test. A total of 2085 differentially expressed miRNAs were detected, among which 433 miRNAs showed differential expression in the T1 group compared to the W1 group; 344 miRNAs showed differential expression in the T2 group compared to the W2 group; 107 miRNAs showed differential expression in the T3 group compared to the W3 group. After combining data from all three patients, 10 miRNAs showed differential expression in the collapse area (T1+T2+T3) compared to the non-collapse area (W1+W2+W3). Compared to the normal area, has-miR-195-5p showed the most significant downregulation. Expression results from RT-PCR revealed that the expression of hsa-miR-195-5p in the collapse area (T1+T2+T3) was significantly lower than that in the non-collapse area (W1+W2+W3) and normal area (Z1+Z2+Z3). 157 genes were perdicted as the target gene of hsa-miR-195-5p.Materials and MethodsFemoral heads of three patients (2 males and 1 female) treated by total hip arthroplasty surgery for steroid-induced femoral head osteonecrosis were selected based on inclusion and exclusion criteria. Bone tissue samples were obtained from the collapse area (T), non-collapse area (W), and normal area (Z) according to the anatomical structure of osteonecrotic femoral heads. Total RNA was extracted from the samples and the microarray chip was scanned. miRNAs showing differential expressions of more than 1.5-fold were selected and was validated by RT-PCR. TargetScan, mirBase and miRanda bioinformatics software was used to predict target genes and identify possible pathways involving these genes.ConclusionsmiR-195-5p showed the most significant difference in the collapse area of osteonecrotic femoral heads, suggesting that collapse may be related to the downregulation of miR-195-5p.

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Section: Discussionmentioning

confidence: 99%

Differential expression of miR-195-5p in collapse of steroid-induced osteonecrosis of the femoral head

Pei

et al. 2017

Oncotarget

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“…The progression of ONFH frequently involves the collapse of the subchondral bone during remodeling with subsequent deformity of the femoral head, often leading to end‐stage osteoarthritis and, eventually, to hip arthroplasty . Risk factors for ONFH include trauma, long‐term steroid treatment, and alcoholism . Recent studies demonstrated that ischemia, caused by interruption of the blood supply to the femoral head, is a primary cause of ONFH .…”

Section: Patient Demographics and Harris Hip Score (Hhs)mentioning

confidence: 99%

Peripheral Blood Stem Cell Therapy Does Not Improve Outcomes of Femoral Head Osteonecrosis With Cap‐Shaped Separated Cartilage Defect

Ying

Wang

Ding

et al. 2019

Journal Orthopaedic Research

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A combination treatment with porous tantalum rod implantation and intra-arterial infusion of peripheral blood stem cells (PBSCs) provides a promise for treating early and intermediate stages of osteonecrosis of the femoral head (ONFH). However, its clinical indications and application restrictions remain unclear. This study aims to determine the clinical, histological, and radiological outcomes of a combination treatment using mechanical support and a targeted intra-arterial infusion of PBSCs for painful ONFH with a capshaped separation (CSS) cartilage defect. Compared with the standard pain management (control group), this combination treatment did not improve the Harris Hip Score (HHS) at 36 months. Micro-CT and histologic analyses showed severe focal destruction in all CSS-ONFH femoral heads in both the combination and control groups. Femoral heads showed a higher percentage of bone lesions in the combination treatment group than in the control group. There was no significant difference in osteoclast number in the subchondral bone areas between the two groups. A high level of expression of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, was detected in blood vessels around the subchondral bone in both groups. The RANKL/OPG (receptor activator of the nuclear factor-kB ligand/osteoprotegerin) ratio was also similar between the control and combination treatment groups. Our results indicate that this combination treatment is not an effective method for the treatment of patients with painful CSS-ONFH. Moreover, this combination treatment did not inhibit inflammatory osteoclastogenesis in patients with more advanced disease.

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“…Viable transplantation studies show that MMP‐9 may be involved in bone regeneration mediated by stem cells (Mosig et al., ). In our previous study, we have demonstrated that MMP‐8,MMP‐9 single‐nucleotide polymorphisms are related to steroid‐induced ONFH in Chinese population (Du, Jin, et al., ; Du, Lin, et al., ).…”

Section: Introductionmentioning

confidence: 96%

MMP‐14 single‐nucleotide polymorphisms are related to steroid‐induced osteonecrosis of the femoral head in the population of northern China

Wang

Sun

et al. 2018

Molec Gen & Gen Med

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Background Osteonecrosis of the femoral head ( ONFH ) is a refractory disease which frequently occurs in young and middle‐aged people. Recent studies indicated that MMP ‐14 played an important role in the development of chondrocytes, metabolism of osteoblasts as well as fate decision of hypertrophic chondrocytes. The aim of this study was to investigate the association between polymorphisms of MMP ‐14 and steroid‐induced osteonecrosis of the femoral head in the Chinese population. Methods We selected 7 SNP s (rs3751488, rs1003349, rs1042703, rs2236302, rs1042704, rs2236303, and rs2236304) on gene MMP ‐14 . Odds ratios ( OR s) and 95% confidence intervals ( CI s) were estimated using the chi‐squared test, genetic model analysis, haplotype analysis, and stratification analysis. Results We discovered that the genotype “G/G” of rs2236302 was associated with ONFH risk in the MMP ‐14 in the codominant model ( OR = 8.62, 95% CI = 1.07–69.46, p = 0.038) and recessive model ( OR = 8.86, 95% CI = 1.10–71.31, p = 0.013). Conclusions We have confirmed that the susceptive SNP s (rs2236302) of MMP ‐14 from the MMP s/ TIMP s system exhibit a significant association with increased risk of steroid‐induced ONFH in the population of northern China.

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A single-nucleotide polymorphism inMMP9is associated with decreased risk of steroid-induced osteonecrosis of the femoral head

Cited by 21 publications

References 36 publications

Differential expression of miR-195-5p in collapse of steroid-induced osteonecrosis of the femoral head

Differential expression of miR-195-5p in collapse of steroid-induced osteonecrosis of the femoral head

Peripheral Blood Stem Cell Therapy Does Not Improve Outcomes of Femoral Head Osteonecrosis With Cap‐Shaped Separated Cartilage Defect

MMP‐14 single‐nucleotide polymorphisms are related to steroid‐induced osteonecrosis of the femoral head in the population of northern China

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