Basic calcium phosphate crystal-induced collagenase production: Role of intracellular crystal dissolution

Geraldine M. McCarthy, Herman S. Cheung, Susan M. Abel, Lawrence M. Ryan

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Objective: To investigate the potential therapeutic effects of inhibiting intracellular dissolution of basic calcium phosphate (BCP) crystals in tissue culture by raising lysosomal pH using bafilomycin A1, a specific vacuolar pump inhibitor. Design: 45Ca-labeled crystals were used to demonstrate intracellular crystal dissolution in human foreskin fibroblasts (HF). Mitogenesis was evaluated using [3H]thymidine incorporation assays and cell counts. Northern blot and Western blot were used to study collagenase [matrix metalloproteinase-1 (MMP1)] mRNA accumulation and protein secretion, respectively. Results: Bafilomycin A1 inhibited intracellular dissolution of BCP crystals and caused a concentration-dependent inhibition of BCP crystal-induced mitogenesis. Doses of bafilomycin A, which inhibited intracellular crystal dissolution and mitogenesis had no effect on BCP crystal-induced MMP1 mRNA accumulation or protein secretion. Conclusion: Raising lysosomal pH to inhibit intracellular BCP crystal dissolution attenuates the proliferative response to BCP crystals in HF but does not prevent metalloprotease synthesis and secretion. The therapeutic potential of lysosomotropic agents for preventing joint destruction in BCP crystal deposition disease is limited.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalOsteoarthritis and Cartilage
Volume6
Issue number3
DOIs
StatePublished - May 1998

Keywords

  • Bafilomycin A1
  • Collagenase
  • Hydroxyapatite
  • Mitogenesis

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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