Quantitative genetic study of the circulating osteopontin in community-selected families

Ermakov, Sergey; Leonov, Andrey; Trofimov, Svetlana; Malkin, Ida; Livshits, Gregory

doi:10.1007/s00198-010-1451-7

Cited by 5 publications

(4 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been demonstrated that OPN plasma concentration shows a familial aggregation in healthy Caucasian individuals [32], and that OPN serum levels are correlated with OPN SNPs in healthy individuals [32,[13][14][15]. In particular, a significant association between the ϩ1239C allele and high OPN serum level was observed in healthy controls by our group [13,14] and in male SLE patients by Kariuki et al [24].…”

Section: Discussionmentioning

confidence: 72%

Association of osteopontin regulatory polymorphisms with systemic sclerosis

et al. 2011

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 72%

Association of osteopontin regulatory polymorphisms with systemic sclerosis

et al. 2011

View full text Add to dashboard Cite

“…However, two recent publications point to a more complex regulation of secreted OPN. Biros et al [19] showed that an intronic polymorphism in the TGFBR2 gene, and Ermakov et al [22] showed that a polymorphism in the promoter region of the integrin-binding sialoprotein gene ( IBSP ) is positively associated with OPN level. Further studies are needed to explore the molecular and physiological mechanisms underlying OPN plasma level.…”

Section: Discussionmentioning

confidence: 99%

TGFBR2 but not SPP1 genotype modulates osteopontin expression in Duchenne muscular dystrophy muscle

Piva

Gavassini

Bello

et al. 2012

The Journal of Pathology

View full text Add to dashboard Cite

A polymorphism (rs28357094) in the promoter region of the SPP1 gene coding for osteopontin (OPN) is a strong determinant of disease severity in Duchenne muscular dystrophy (DMD). The rare G allele of rs28357094 alters gene promoter function and reduces mRNA expression in transfected HeLa cells. To dissect the molecular mechanisms of increased disease severity associated with the G allele, we characterized SPP1 mRNA and protein in DMD muscle biopsies of patients with defined rs28357094 genotype. We did not find significant differences in osteopontin mRNA or protein expression between patients carrying the T (ancestral allele) or TG/GG genotypes at rs28357094. The G allele was significantly associated with reduced CD4+ and CD68+ cells on patient muscle biopsy. We also quantified transforming growth factor-β (TGFB) and TGFB receptor-2 (TGFBR2) mRNA in DMD muscle biopsies, given the ability of TGFB and TGFBR2 to activate SPP1 promoter region and their role in DMD pathogenesis. The amount of TGFB and TGFBR2 mRNA did not predict the amount of SPP1 mRNA or protein, while a polymorphism in the TGFBR2 gene (rs4522809) was found to be a strong predictor of SPP1 mRNA level. Our findings suggest that OPN mediates inflammatory changes in DMD and that TGFB signalling has a role in the complex regulation of osteopontin expression.

show abstract

“…Chondrocytes in the first passage were seeded in 24-well plates at a starting density of 1x10 4 cells/well, until confluency was achieved. Next, the cell population was divided into three groups: i) The control group, maintained as unstimulated and untreated control cells; ii) the normal concentration (N-OPN) group that were treated with 100 ng/ml OPN (R&D Systems, Inc., Minneapolis, MN, USA) for 48 h, which was within the normal circulating concentration range (2.3-200 ng/ml) described in previous studies (12,(16)(17)(18)(19); and iii) the high concentration (H-OPN) group, treated with 1 µg/ml OPN for 48 h.…”

Section: Methodsmentioning

confidence: 99%

Effect of osteopontin on the mRNA expression of ADAMTS4 and ADAMTS5 in chondrocytes from patients with knee osteoarthritis

Gao

Zeng

Song

et al. 2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Previous studies have demonstrated that osteopontin (OPN) levels are elevated in the synovial fluid and articular cartilage, and are associated with the severity of knee osteoarthritis (OA). However, the role of OPN in the pathogenesis of OA has yet to be elucidated. The present study aimed to investigate the effects of OPN on the expression of the aggrecanases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5, in human OA chondrocytes, as they serve a key function in aggrecan degradation. Human OA chondrocytes were obtained from the knees of 16 patients with OA, and subsequently cultured in a monolayer. The chondrocytes were divided into three groups, which included the control (no treatment), N-OPN (treated with 100 ng/ml OPN, the normal circulating OPN concentration) and the H-OPN groups (treated with 1 µg/ml OPN, a high OPN concentration). Reverse transcription-quantitative polymerase chain reaction was performed to quantify the relative mRNA expression levels of ADAMTS4, ADAMTS5 and aggrecan in the chondrocytes. The mRNA expression levels of ADAMTS4 were significantly reduced in the N-OPN and H-OPN groups when compared with the control group (P<0.0001). In addition, the mRNA expression levels of ADAMTS4 were lower in the H-OPN group when compared with the N-OPN group (P<0.001). However, no statistically significant difference was observed in the relative mRNA expression levels of ADAMTS5 among the three groups (P>0.05). Furthermore, the mRNA expression levels of aggrecan were higher in the N-OPN and H-OPN groups when compared with the control group (P<0.0001), and a statistically significant difference was observed between the N-OPN and H-OPN groups with regard to the mRNA expression of aggrecan (P<0.0001). These results demonstrated that OPN may exert a protective effect in human OA chondrocytes against aggrecan degradation by suppressing the expression of ADAMTS4. IntroductionOsteoarthritis (OA) is the most common degenerative disorder of the joint, which is characterized by the progressive loss of articular cartilage. This loss is attributed primarily to the proteolysis of certain structural components within the extracellular matrix (ECM), including proteoglycans and collagens (1-3). Aggrecan is a major component of the cartilage-specific proteoglycans. A number of studies have indicated that the aggrecanase-mediated degradation of aggrecan is a crucial factor in the development of OA (4-7). Aggrecanases are members of the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, which includes ADAMTS1, 4, 5, 8, 9 and 15, that are expressed in the articular cartilage tissues and chondrocytes of numerous animal species, in addition to humans (8). A previous study indicated that ADAMTS4 and ADAMTS5 were responsible for aggrecan degradation in a human model of OA (9).Osteopontin (OPN) is an ECM glycoprotein that is hypothesized to be a potential inflammatory cytokine. OPN, as a biomarker, has been studied in vivo in rats (10), in healthy h...

show abstract

Quantitative genetic study of the circulating osteopontin in community-selected families

Abstract: Further studies are required to confirm the observed results and to explore the underlying molecular and physiological mechanisms.

Cited by 5 publications

References 46 publications

Association of osteopontin regulatory polymorphisms with systemic sclerosis

Association of osteopontin regulatory polymorphisms with systemic sclerosis

TGFBR2 but not SPP1 genotype modulates osteopontin expression in Duchenne muscular dystrophy muscle

Effect of osteopontin on the mRNA expression of ADAMTS4 and ADAMTS5 in chondrocytes from patients with knee osteoarthritis

Contact Info

Product

Resources

About