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 journalArticle

25 Citations (Scopus)

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
Pages (from-to)205-213
Number of pages9
JournalOsteoarthritis and Cartilage
Volume6
Issue number3
DOIs
StatePublished - May 1 1998

Fingerprint

Calcium phosphate
Collagenases
Dissolution
Crystals
Foreskin
Matrix Metalloproteinase 1
Fibroblasts
Messenger RNA
Metalloproteases
Therapeutic Uses
calcium phosphate
Northern Blotting
Proteins
Thymidine
Tissue culture
Cell Count
Joints
Western Blotting
Assays
Pumps

Keywords

  • Bafilomycin A1
  • Collagenase
  • Hydroxyapatite
  • Mitogenesis

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Basic calcium phosphate crystal-induced collagenase production : Role of intracellular crystal dissolution. / McCarthy, Geraldine M.; Cheung, Herman S; Abel, Susan M.; Ryan, Lawrence M.

In: Osteoarthritis and Cartilage, Vol. 6, No. 3, 01.05.1998, p. 205-213.

Research output: Contribution to journalArticle

McCarthy, Geraldine M. ; Cheung, Herman S ; Abel, Susan M. ; Ryan, Lawrence M. / Basic calcium phosphate crystal-induced collagenase production : Role of intracellular crystal dissolution. In: Osteoarthritis and Cartilage. 1998 ; Vol. 6, No. 3. pp. 205-213.
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