Production of tissue inhibitor of metalloproteinases 3 is selectively enhanced by calcium pentosan polysulfate in human rheumatoid synovial fibroblasts

Takizawa M, Ohuchi E, Yamanaka H, Nakamura H, Ikeda E, Ghosh P, Okada Y · Arthritis and Rheumatism

PPS raised production of TIMP-3 — the one endogenous inhibitor that blocks the aggrecanases — dose-dependently and selectively, leaving seven matrix metalloproteinases and the other three TIMPs untouched. The increase was translational rather than transcriptional, and was larger when the cells were inflamed.

Population

Human rheumatoid synovial fibroblasts and synovial tissue

Intervention

Calcium PPS at 0.1, 1 and 10 µg/ml, with and without interleukin-1α

Comparator

Untreated and cytokine-only cultures

Limitations

Rheumatoid rather than osteoarthritic synovium, cultured cells; PPS's developer is a co-author; the concentrations span the range achievable in synovial fluid but were applied continuously, unlike a weekly injection.