Dataset Information

Methylation of the OP-1 promoter: potential role in the age-related decline in OP-1 expression in cartilage.

ABSTRACT: OBJECTIVE:An age-related decline in chondrocyte production of osteogenic protein-1 (OP-1) (Bone Morphogenetic Protein-7) may contribute to cartilage loss in osteoarthritis. This study was designed to determine if increased methylation of the OP-1 promoter might serve as a mechanism for the age-related decline in OP-1 expression. METHODS:Human articular chondrocytes were isolated from cartilage obtained after death from tissue donors (ages 19-86 years) without a known history of arthritis. DNA was obtained from isolated chondrocytes in primary culture and analyzed for OP-1 promoter methylation by polymerase chain reaction (PCR) after bisulfite treatment. Cultured cells were treated with the DNA methyltransferase inhibitor 5-azacytidine and OP-1 production was measured in the media by enzyme-linked immunosorbent assay (ELISA). RNA was isolated to measure expression of insulin-like growth factor-1 (IGF-1), the IGF-1 receptor (IGF-1R), aggrecan, and OP-1 by real-time PCR. RESULTS:Methylation of the OP-1 promoter was detected in chondrocytes isolated from tissue obtained from older adults and there was a positive correlation between age and OP-1 methylation status (n=22, R(2)=0.277, P=0.014). Inhibition of methylation in cultured cells with 5-azacytidine increased chondrocyte production of OP-1 protein and increased the expression of the IGF-1, the IGF-1R, aggrecan, and OP-1 genes but not GAPDH. CONCLUSION:Age-related methylation of the OP-1 promoter may contribute to a decrease in OP-1 production in cartilage and a decrease in expression of OP-1 responsive genes such as IGF-1, the IGF-1R, and aggrecan.

SUBMITTER: Loeser RF

PROVIDER: S-EPMC2692619 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Methylation of the OP-1 promoter: potential role in the age-related decline in OP-1 expression in cartilage.

Loeser R F RF Im H-J HJ Richardson B B Lu Q Q Chubinskaya S S

Osteoarthritis and cartilage 20080930 4

<h4>Objective</h4>An age-related decline in chondrocyte production of osteogenic protein-1 (OP-1) (Bone Morphogenetic Protein-7) may contribute to cartilage loss in osteoarthritis. This study was designed to determine if increased methylation of the OP-1 promoter might serve as a mechanism for the age-related decline in OP-1 expression.<h4>Methods</h4>Human articular chondrocytes were isolated from cartilage obtained after death from tissue donors (ages 19-86 years) without a known history of ar ...[more]

PMID: 18829350

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Dataset Information

Methylation of the OP-1 promoter: potential role in the age-related decline in OP-1 expression in cartilage.

Publications

Methylation of the OP-1 promoter: potential role in the age-related decline in OP-1 expression in cartilage.

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