Retinoic acid stimulates pyrophosphate elaboration by cartilage and chondrocytes. Calcif Tissue Int 1996 Aug;59(2):128-33
Date
08/01/1996Pubmed ID
8687982DOI
10.1007/s002239900099Scopus ID
2-s2.0-0029683759 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Abnormal metabolism of extracellular inorganic pyrophosphate (PPi) by articular cartilage contributes to calcium pyrophosphate dihydrate (CPPD) crystal formation and the resultant arthritis known as CPPD deposition disease. The factors causing excess PPi elaboration in affected cartilage remain poorly defined. Retinoic acid (RA), a naturally occurring vitamin A metabolite, promotes cartilage degeneration and mineralization, two correlates of CPPD crystal deposition. RA was examined as a potential modifier of cartilage PPi elaboration. All-trans RA (200-1000 nM) increased PPi levels in culture medium of normal porcine cartilage and chondrocytes 2-3-fold over control values at 96 hours of incubation (P < 0.01). IGF1 and anti-EGF antibody diminished the effects of RA on PPi elaboration. RA modestly increased activity of the PPi-generating ectoenzyme NTPPPH in culture medium (P < 0.01). As some RA effects are mediated through increased activity of TGFbeta, a known PPi stimulant, we examined the effect of anti-TGFbeta antibody on RA-induced PPi elaboration. PPi levels in medium were reduced from 30 +/- 7 microM in cartilage cultures with 500 nM RA to 14 +/- 4 microM PPi in cartilage cultures with RA and anti-TGFbeta. Anti-TGFbeta antibody, however, had no significant effect on RA-induced PPi elaboration in chondrocyte cultures. Thus, RA, along with TGFbeta and ascorbate, can now be included in the list of known PPi stimulants. All three of these factors promote mineralization in growth plate cartilage. These data support a central role for TGFbeta in CPPD disease, and provide further evidence linking processes of normal and pathologic calcification in cartilage.
Author List
Rosenthal AK, Henry LAAuthor
Ann K. Rosenthal MD Associate Dean, Chief, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntibodies, Monoclonal
Arthritis
Calcinosis
Calcium Pyrophosphate
Cartilage, Articular
Cells, Cultured
Insulin-Like Growth Factor I
Keratolytic Agents
Knee Joint
Organ Culture Techniques
Pyrophosphatases
Swine
Transforming Growth Factor beta
Tretinoin