Faculty Collaboration Database

Basic calcium phosphate crystal-induced collagenase production: role of intracellular crystal dissolution. Osteoarthritis Cartilage 1998 May;6(3):205-13

Date

07/31/1998

Pubmed ID

9682787

DOI

10.1053/joca.1998.0113

Scopus ID

2-s2.0-0032076279 (requires institutional sign-in at Scopus site)   32 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 A1 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.

Author List

McCarthy GM, Cheung HS, Abel SM, Ryan LM

MESH terms used to index this publication - Major topics in bold

Anti-Bacterial Agents
Blotting, Northern
Calcium Phosphates
Cells, Cultured
Collagenases
Crystallization
Dose-Response Relationship, Drug
Fibroblasts
Humans
Hydrogen-Ion Concentration
Lysosomes
Macrolides
Metalloendopeptidases
Mitosis