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osteonecrosis gene

Yang Song, Zhenwu Du, Qiwei Yang, Ming Ren, Yujie Sui, Qingyu Wang, Ao Wang, Haiyue Zhao, Jincheng Wang, Guizhen Zhang
The critical roles of IGFBP3 in regulating the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells strongly indicate its potential effects on the pathogenesis of osteonecrosis of the femoral head (ONFH). In this study, we investigated the association of IGFBP3 gene polymorphism and its protein expression with the development of ONFH to further explore its molecular pathogenesis. Ligase detection reactions and enzyme-linked immunosorbent assay were used to detect the polymorphisms of rs2453839[C/T] and rs3110697[A/G] and the serum protein expression of IGFBP3 gene in 182 cases and 179 controls, respectively...
October 5, 2016: DNA and Cell Biology
Naga Suresh Adapala, Ryosuke Yamaguchi, Matthew Phipps, Olumide Aruwajoye, Harry K W Kim
In children with Legg-Calvé-Perthes disease, loss of blood supply to the femoral head results in ischemic osteonecrosis. Generally, macrophages play important roles in the inflammatory response to tissue necrosis, but their role in ischemic osteonecrosis of the femoral head (ONFH) is not known. The purpose of this study was to determine the macrophage-inflammatory responses after ONFH and the receptor mechanisms involved in sensing the necrotic bone, using a piglet model of Legg-Calvé-Perthes disease. Induction of ONFH resulted in increased numbers of CD14(+) macrophages (4...
September 17, 2016: American Journal of Pathology
Jieli Du, Wanlin Liu, Tianbo Jin, Zhenqun Zhao, Rui Bai, Huiqin Xue, Junyu Chen, Mingqi Sun, Xiyang Zhang, Guoqiang Wang, Jianzhong Wang
Osteonecrosis of the femoral head (ONFH) is a common hip joint disease, and steroid-induced ONFH accounts for a large number of cases. Here, we examined eight previously-identified single-nucleotide polymorphisms (SNPs) in the MPP2 and MPP9 genes of 285 steroid-induced ONFH patients and 507 healthy controls from northern China to determine whether these SNPs were associated with the risk of developing steroid-induced ONFH. Chi-squared tests and genetic model and haplotype analyses were used to evaluate associations...
September 15, 2016: Oncotarget
Jieli Du, Tianbo Jin, Yuju Cao, Junyu Chen, Yongchang Guo, Mingqi Sun, Jian Li, Xiyang Zhang, Guoqiang Wang, Jianzhong Wang
BACKGROUND: Steroid-induced osteonecrosis of the femoral head (ONFH) is the most common clinical nontraumatic ONFH. Once ONFH occurs, it seriously reduces patients' quality of life. The matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) system was found to play a significant role in the development of ONFH. The aim of this study was to identify the associations between 7 genes selected from the MMP/TIMP system and steroid-induced ONFH. METHODS: We genotyped 34 single-nucleotide polymorphisms (SNPs) of 7 genes selected from the MMP/TIMP system in a case-control study with 285 cases of steroid-induced ONFH and 308 healthy controls...
September 2016: Medicine (Baltimore)
Jie Zhao, Xin-Long Ma, Jian-Xiong Ma, Lei Sun, Bin Lu, Ying Wang, Guo-Sheng Xing, Yan Wang, Ben-Chao Dong, Li-Yan Xu, Ming-Jie Kuang, Lin Fu, Hao-Hao Bai, Yue Ma, Wei-Lin Jin
Steroid-associated osteonecrosis (SAON) is one of the common complications of clinical glucocorticoid (GC) administration, with osteocyte apoptosis appearing as the primary histopathological lesion. However, the precise mechanism underlying SAON remains unknown. Epigenetic modification may be a major cause of SAON. Recently, cumulative research revealed that Ten-Eleven Translocation (TET) proteins can catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and then alter the epigenetic state of DNA...
September 13, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Tae-Ho Kim, Sang-Cheol Bae, Sang-Han Lee, Shin-Yoon Kim, Seung-Hoon Baek
Osteonecrosis of the femoral head (ONFH) is a complex and multifactorial disease that is influenced by a number of genetic factors in addition to environmental factors. Some autoimmune disorders, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are associated with the development of ONFH. Complement receptor type 2 (CR2) is membrane glycoprotein which binds C3 degradation products generated during complement activation. CR2 has many important functions in normal immunity and is assumed to play a role in the development of autoimmune disease...
2016: BioMed Research International
Nataša Karas-Kuželički, Simona Mencej-Bedrač, Janez Jazbec, Janja Marc, Irena Mlinarič-Raščan
Treatment induced non-traumatic osteonecrosis (ON) has been reported increasingly in children treated for acute lymphoblastic leukemia (ALL). Several risk factors for ON have been identified in childhood cancer patients; however, their diagnostic and prognostic power is limited and the etiology of the disease remains unclear. Therefore, a continuous effort is focused on the identification of additional ON risk factors. We performed a retrospective study of 313 childhood ALL patients to test the association between the ON occurrence in children receiving ALL therapy and common polymorphisms in potential target genes: Thiopurine S-methyltransferase (TPMT; 460G>A, 719A>G), 5,10-methylenetetrahydrofolate reductase (MTHFR; 677C>T, 1298A>C), estrogen receptor alpha 1 (ESR1; XbaI) and collagen type I, α1 (COL1A1; Sp1)...
August 2016: Experimental and Therapeutic Medicine
Ning Han, Zengchun Li, Zhengdong Cai, Zuoqin Yan, Yingqi Hua, Chong Xu
P-glycoprotein (P-gp) plays a role in steroid-induced osteonecrosis of the femoral head (ONFH), but the underlying mechanism remains unknown. We hypothesized that P-gp overexpression can prevent ONFH by regulating bone marrow-derived multipotent stromal cell (BMSC) adipogenesis and osteogenesis. BMSCs from Sprague-Dawley rats were transfected with green fluorescent protein (GFP) or the multidrug resistance gene 1 (MDR1) encoding GFP and P-gp. Dexamethasone was used to induce BMSC differentiation. Adipogenesis was determined by measuring peroxisome proliferator-activated receptor (PPAR-γ) expression and the triglyceride level...
July 11, 2016: Journal of Cellular and Molecular Medicine
Ryosuke Yamaguchi, Nobuhiro Kamiya, Naga Suresh Adapala, Hicham Drissi, Harry K W Kim
BACKGROUND: Ischemic osteonecrosis of the femoral head in children is associated with chronic hip synovitis and increased levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in the synovial fluid due to unknown mechanisms. The purpose of this study was to investigate hypoxia-inducible factor-1 (HIF-1) activation as a molecular mechanism linking the induction of ischemic osteonecrosis to IL-6 production and the initiation of hip synovitis. METHODS: Ischemic osteonecrosis was surgically induced in the right femoral head of 6 piglets...
July 6, 2016: Journal of Bone and Joint Surgery. American Volume
Pengfei Li, Nan Sun, Jianchun Zeng, Yirong Zeng, Yueguang Fan, Wenjun Feng, Jie Li
BACKGROUND: Apoptosis of osteoblasts and osteocytes is one cause of steroid-induced osteonecrosis of the femoral head; however, the molecular mechanism of steroid affecting osteoblasts at the genetic level is unclear. The aim of the present work is to examine differential expression of osteoblasts in rats after steroid intervention and to verify expression by real-time polymerase chain reaction (RT-PCR). METHODS: Primary culture, passaging and identification of osteoblasts of SD neonatal rats were conducted; osteoblasts were divided into two groups, the control group, and the steroid group...
October 10, 2016: Gene
Wenyu Wang, Yang Liu, Jingcan Hao, Shuyu Zheng, Yan Wen, Xiao Xiao, Awen He, Qianrui Fan, Feng Zhang, Ruiyu Liu
Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8)...
October 10, 2016: Gene
Yizhou Li, Yuan Wang, Yongchang Guo, Quanjian Wang, Yongri Ouyang, Yuju Cao, Tianbo Jin, Jianzhong Wang
Alcohol-induced osteonecrosis of the femoral head (ONFH) is an important pathogenesis of nontraumatic ONFH. However, the mechanisms of the pathogenesis are still unknown. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) have been implicated in multiple functions including blocking osteoclast maturation, controlling vascular calcifications, and promoting tumor growth and metastasis. The purpose of this article was to explore the association between OPG and RANKL gene variants and alcohol-induced ONFH...
June 2016: Medicine (Baltimore)
Wayne Mah, Swapnil K Sonkusare, Tracy Wang, Bouziane Azeddine, Mihaela Pupavac, Jian Carrot-Zhang, Kwangseok Hong, Jacek Majewski, Edward J Harvey, Laura Russell, Colin Chalk, David S Rosenblatt, Mark T Nelson, Chantal Séguin
BACKGROUND: Osteonecrosis of the femoral head is a debilitating disease that involves impaired blood supply to the femoral head and leads to femoral head collapse. METHODS: We use whole-exome sequencing and Sanger sequencing to analyse a family with inherited osteonecrosis of the femoral head and fluorescent Ca(2+) imaging to functionally characterise the variant protein. RESULTS: We report a family with four siblings affected with inherited osteonecrosis of the femoral head and the identification of a c...
October 2016: Journal of Medical Genetics
G G Song, Y H Lee
OBJECTIVE: The aim of the present study was to determine whether polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are associated with susceptibility to osteonecrosis of the femoral head (ONFH). METHODS: We conducted a meta-analysis to assess the association between the 4b/a, G894T, and T786C polymorphisms of eNOS and the susceptibility to ONFH. RESULTS: A total of five studies, which included 566 cases and 833 controls, were included in the meta-analysis...
June 16, 2016: Zeitschrift Für Rheumatologie
Toshikazu Kubo, Keiichiro Ueshima, Masazumi Saito, Masashi Ishida, Yuji Arai, Hiroyoshi Fujiwara
BACKGROUND: Steroid (glucocorticoid)-induced osteonecrosis of the femoral head (ONFH) in young adults has been a challenging disorder due to frequent incidence of collapse of the femoral head and resulting dysfunction of the hip joint and impairing quality of life. In Japan, the working group on ONFH in the Specific Disease Investigation Committee under auspices of the Japanese Ministry of Health, Labor and Welfare was founded in 1975, clinical and related basic research on ONFH have been continued for more than 40 years...
July 2016: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
Naga Suresh Adapala, Harry K W Kim
OBJECTIVE: Ischemic osteonecrosis of the femoral head (ONFH) in piglets results in an ischemic injury to the immature articular cartilage. The molecular changes in the articular cartilage in response to ONFH have not been investigated using a transcriptomic approach. The purpose of this study was to perform a genome-wide transcriptomic analysis to identify genes that are upregulated in the immature articular cartilage following ONFH. METHODS: ONFH was induced in the right femoral head of 6-week old piglets...
2016: PloS One
Xiao Ji, Xiang Chen, Xijie Yu
Abnormal osteoclast formation and resorption play a fundamental role in osteoporosis pathogenesis. Over the past two decades, much progress has been made to target osteoclasts. The existing therapeutic drugs include bisphosphonates, hormone replacement therapy, selective estrogen receptor modulators, calcitonin and receptor activator of nuclear factor NF-κB ligand (RANKL) inhibitor (denosumab), etc. Among them, bisphosphonates are most widely used due to their low price and high efficiency in reducing the risk of fracture...
2016: International Journal of Molecular Sciences
Cheng Hao, Shuhua Yang, Weihua Xu, Jacson K Shen, Shunan Ye, Xianzhe Liu, Zhe Dong, Baojun Xiao, Yong Feng
Steroid-induced osteonecrosis of femoral head (ONFH) is a serious complication of glucocorticoid (GC) use. We investigated the differential expression of miRs in the mesenchymal stem cells (MSCs) of patients with ONFH, and aimed to explain the relationship between GC use and the development of MSC dysfunction in ONFH. Cells were collected from bone marrow of patients with ONFH. Samples were assigned to either GCs Group or Control Group at 1:1 matched with control. We then used miRNA microarray analysis and real-time PCR to identify the differentially expressed miRs...
2016: Scientific Reports
Laura López-Delgado, Leyre Riancho-Zarrabeitia, José A Riancho
INTRODUCTION: Osteoporosis is a highly prevalent skeletal disorder characterized by compromised bone strength, usually related to decreased bone mass and microstructural alterations of bone tissue, predisposing a person to an increased risk of fracture. As other prevalent disorders, osteoporosis is the result of a complex interplay of genetic and acquired factors. AREAS COVERED: We provide an update of recent studies aimed at identifying the clinical and genetic factors that influence the response to drugs used to treat osteoporosis, as well as those determining the risk of two intriguing adverse effects of antiresorptives: osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF)...
2016: Expert Opinion on Drug Metabolism & Toxicology
Guo Ju Hong, Nuan Lin, Lei Lei Chen, Xiao Bo Chen, Wei He
Emerging evidence has shown that vascular endothelial growth factor (VEGF) gene polymorphisms are the key initiators that regulate the expression of the VEGF protein, which has a vital role in osteonecrosis of the femoral head (ONFH). The aim of the present study was to investigate whether polymorphisms of the VEGF genes are associated with the occurrence of ONFH. A comprehensive search was performed on MEDLINE, Embase, Web of Science and China National Knowledge Infrastructure databases before June 2015. Meta-analyses were carried out for the VEGF gene -634G/C polymorphisms (single-nucleotide polymorphism with 3 eligible studies)...
January 2016: Biomedical Reports
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