Abstract
This study sought to examine the expression of genes implicated in phosphate transport and pathological calcification in osteoarthritis (OA) and rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and investigate the biological effects of phosphate. Results revealed that several genes, which were implicated in phosphate transport and pathological calcification, were differentially expressed in OA FLS and RA FLS. Phosphate stimulated the expression of matrix metalloproteinse-1, matrix metalloproteinse-3, cyclooxygenase-2, and interleukin-1βin a dose-dependent manner. Phosphate also induced OA FLS cell death but not RA FLS cell death at higher concentration. Calcification inhibitors, phosphocitrate (PC), and ethane-1-hydroxy-1,1-diphosphonate (EHDP), effectively inhibited these detrimental biological effects of phosphate. These findings suggest that abnormal expression of genes implicated in phosphate transport and pathological calcification may contribute to the progression of OA through the induction of extracellular matrix-degrading enzymes, proinflammatory cytokines, cell death, and calcium deposits. Calcification inhibitors such as PC and EHDP are potent inhibitors of these detrimental biological effects of phosphate.
Highlights
Osteoarthritis (OA) is characterized by the degeneration of articular cartilage
Calcium phosphate crystals were found in the synovial fluid of up to 26% of the patients with rheumatoid arthritis (RA), and a worse clinical outcome was associated with the presence of these crystals [4]
We have recently carried out a microarray analysis of hTERT-OA 13A fibroblast-like synoviocytes (FLS) and hTERTRA 516 FLS and found that several genes implicated in lipid transfer, phosphate transport, or pathological calcification were differentially expressed in OA and RA FLS cell lines hTERT-OA 13A FLS and hTERT-RA 516 FLS [16]
Summary
Osteoarthritis (OA) is characterized by the degeneration of articular cartilage. the precise biochemical events that initiates OA are not well understood, many risk or contributory factors have been identified including aging, obesity, and pathological calcification. Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPPD) crystals are the two most common forms of articular calcium phosphate crystals These crystals are found in the synovial fluid of the patients with OA, and their presence in the synovial fluid correlates with the radiographic evidence of cartilaginous degeneration [1,2,3]. BCP and CPPD crystals stimulate the expression of matrix metalloproteinases (MMPs), mitogenesis, and endocytotic activity of cells in monolayer culture [5, 6]. These crystals may alter the biomechanical properties of menisci and articular cartilage [7].
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