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

R. F. Loeser, H. J. Im, B. Richardson, Q. Lu, S. Chubinskaya

Research output: Contribution to journalArticlepeer-review


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, R2 = 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.

Original languageEnglish (US)
Pages (from-to)513-517
Number of pages5
JournalOsteoarthritis and Cartilage
Issue number4
StatePublished - Apr 2009
Externally publishedYes


  • Aging
  • Chondrocyte
  • Growth factors
  • Osteoarthritis

ASJC Scopus subject areas

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine


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