Association of SPP1 promoter variants with hip osteoarthritis susceptibility in Chinese population

Lv, Chuanjian; Li, Yan; Xu, Jian; Cao, Huichun; Li, Xiaoxiao; Ma, Bo; Ning, Peigang; Wang, Yan; Wang, Meiyun; Zhu, Shu; Ge, Yinghui; Huang, Suizhu; Jin, Yi

doi:10.1016/j.gene.2015.03.036

Cited by 7 publications

(6 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Osteopontin (or SPP1) is a member of the small integrin‐binding ligand N‐liked glycol‐proteins, which are known to regulate the reabsorption of biological processes, bone matrix connection, and bone matrix mineralization (Liang et al, ). And recent evidence has shown that genetic variant rs17524488 in the promoter of SPP1 gene affected transcriptional activity of SPP1, thus conferring an elevated risk for diseases, including hip OA via enhance of SPP1 expression (Lv et al, ). Thus, we may come to a conclusion that upregulation of miR‐186 or knockdown of SPP1 may suppress chondrocyte apoptosis and advance chondrocyte proliferation.…”

Section: Discussionmentioning

confidence: 99%

microRNA‐186 inhibition of PI3K–AKT pathway via SPP1 inhibits chondrocyte apoptosis in mice with osteoarthritis

Zeng

Tian

Huang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Chondrocyte apoptosis has been implicated as a major pathological osteoarthritis (OA) change in humans and experimental animals. We evaluate the ability of miR-186 on chondrocyte apoptosis and proliferation in OA and elucidate the underlying mechanism concerning the regulation of miR-186 in OA. Gene expression microarray analysis was performed to screen differentially expressed messenger RNAs (mRNAs) in OA. To validate the effect of miR-186 on chondrocyte apoptosis, we upregulated or downregulated endogenous miR-186 using mimics or inhibitors. Next, to better understand the regulatory mechanism for miR-186 governing SPP1, we suppressed the endogenous expression of SPP1 by small interfering RNA (siRNA) against SPP1 in chondrocytes. We identified SPP1 is highly expressed in OA according to an mRNA microarray data set GSE82107. After intra-articular injection of papain into mice, the miR-186 is downregulated while the SPP1 is reciprocal, with dysregulated PI3K-AKT pathway in OA cartilages. Intriguingly, miR-186 was shown to increase chondrocyte survival, facilitate cell cycle entry in OA chondrocytes, and inhibit chondrocyte apoptosis in vitro by modulation of pro-and antiapoptotic factors. The determination of luciferase activity suggested that miR-186 negatively targets SPP1. Furthermore, we found that the effect of miR-186 suppression on OA chondrocytes was lost when SPP1 was suppressed by siRNA, suggesting that miR-186 affected chondrocytes by targeting and depleting SPP1, a regulator of PI3K-AKT pathway. Our findings reveal a novel mechanism by which miR-186 inhibits chondrocyte apoptosis in OA by interacting with SPP1 and regulating PI3K-AKT pathway. Restoring miR-186 might be a future therapeutic strategy for OA. K E Y W O R D S apoptosis, chondrocyte, microRNA-186, osteoarthritis, PI3K-AKT pathway, proliferation, SPP1

show abstract

Section: Discussionmentioning

confidence: 99%

microRNA‐186 inhibition of PI3K–AKT pathway via SPP1 inhibits chondrocyte apoptosis in mice with osteoarthritis

Zeng

Tian

Huang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…qRT-PCR was conducted to validate the accuracy of microarray data using an independent sample of eight patients with NFH and eight healthy controls (Table 1 ). Based on gene function and results from previous study of joint diseases, nine cartilage development and damage-related differently expressed genes in the microarray experiment were selected for qRT-PCR validation, including ANGPTL4, ASPN , COL1A1 , COL3A1 , CRTAC1 , OGN , P4HA2 , SPP1 and VKORC1 [ 13 – 20 ]. Glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ) was used as an endogenous invariant control for data normalization.…”

Section: Methodsmentioning

confidence: 99%

Comparative analysis of gene expression profiles in normal hip human cartilage and cartilage from patients with necrosis of the femoral head

Liu

Wang

et al. 2016

Arthritis Res Ther

View full text Add to dashboard Cite

BackgroundThe pathogenesis of necrosis of the femoral head (NFH) remains elusive. Limited studies were conducted to investigate the molecular mechanism of hip articular cartilage damage in NFH. We conducted genome-wide gene expression profiling of hip articular cartilage with NFH.MethodsHip articular cartilage specimens were collected from 18 NFH patients and 18 healthy controls. Gene expression profiling of NFH articular cartilage was carried out by Agilent Human 4x44K Gene Expression Microarray chip. Differently expressed genes were identified using the significance analysis of microarrays (SAM) software. Gene Ontology (GO) enrichment analysis of differently expressed genes was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Significantly differently expressed genes in the microarray experiment were selected for quantitative real-time PCR (qRT-PCR) and immunohistochemical validation.ResultsSAM identified 27 differently expressed genes in NFH articular cartilage, functionally involved in extracellular matrix, cytokines, growth factors, cell cycle and apoptosis. The expression patterns of the nine validation genes in qRT-PCR were consistent with that in proteinaceous extracellular matrix (false discovery rate (FDR) = 3.22 × 10-5), extracellular matrix (FDR = 5.78 × 10-5), extracellular region part (FDR = 1.28 × 10-4), collagen (FDR = 3.22 × 10-4), extracellular region (FDR = 4.78 × 10-4) and platelet-derived growth factor binding (FDR = 5.23 × 10-4).ConclusionsThis study identified a set of differently expressed genes, implicated in articular cartilage damage in NFH. Our study results may provide novel insight into the pathogenesis and rationale of therapies for NFH.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0991-4) contains supplementary material, which is available to authorized users.

show abstract

“…Conversely, there are investigations that associate SPP1 SNP with RA susceptibility, joint destruction, the course of oligoarticular onset juvenile idiopathic arthritis (JIA), and the positivity to anti-citrullinated protein antibodies (ACPA) [ 154 , 155 , 156 , 157 ]. Concerning OA, most studies associate SPP1 genotype carriage with OA development risk and radiographic severity [ 72 , 158 , 159 , 160 ]. Regarding SPP1 variations, it is essential to note that differences are detected between populations in the same, for instance, rs11730582; this may be related to environmental factors, lifestyles, and genetic backgrounds that determine susceptibility to diseases.…”

Section: Osteopontin: Could It Be Considered a Common Denominator In ...mentioning

confidence: 99%

Osteopontin: A Bone-Derived Protein Involved in Rheumatoid Arthritis and Osteoarthritis Immunopathology

et al. 2023

View full text Add to dashboard Cite

Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) glycoprotein that plays a critical role in bone remodeling. Therefore, it is an effector molecule that promotes joint and cartilage destruction observed in clinical studies, in vitro assays, and animal models of RA and OA. Since OPN undergoes multiple modifications, including posttranslational changes, proteolytic cleavage, and binding to a wide range of receptors, the mechanisms by which it produces its effects, in some cases, remain unclear. Although there is strong evidence that OPN contributes significantly to the immunopathology of RA and OA when considering it as a common denominator molecule, some experimental trial results argue for its protective role in rheumatic diseases. Elucidating in detail OPN involvement in bone and cartilage degeneration is of interest to the field of rheumatology. This review aims to provide evidence of the OPN’s multifaceted role in promoting joint and cartilage destruction and propose it as a common denominator of AR and OA immunopathology.

show abstract

Association of SPP1 promoter variants with hip osteoarthritis susceptibility in Chinese population

Cited by 7 publications

References 40 publications

microRNA‐186 inhibition of PI3K–AKT pathway via SPP1 inhibits chondrocyte apoptosis in mice with osteoarthritis

microRNA‐186 inhibition of PI3K–AKT pathway via SPP1 inhibits chondrocyte apoptosis in mice with osteoarthritis

Comparative analysis of gene expression profiles in normal hip human cartilage and cartilage from patients with necrosis of the femoral head

Osteopontin: A Bone-Derived Protein Involved in Rheumatoid Arthritis and Osteoarthritis Immunopathology

Contact Info

Product

Resources

About