Retinoic acid stimulates pyrophosphate elaboration by cartilage and chondrocytes
Retinoic acid stimulates pyrophosphate elaboration by cartilage and chondrocytes
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DOI：
10.1007/s002239900099
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发表时间：
1996-08-01
影响因子：
4.2
通讯作者：
Henry, LA
中科院分区：
文献类型：
--
作者：
Rosenthal, AK;Henry, LA
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 TGF beta, a known PPi stimulant. we examined the effect of anti-TGF beta antibody on RA-induced PPi elaboration. PPi levels in medium were reduced from 30 +/- 7 mu M in cartilage cultures with 500 nM RA to 14 +/- 4 mu M PPi in cartilage cultures with RA and anti-TGF beta. Anti-TGF beta antibody. however, had no significant effect on RA-induced PPi elaboration in chondrocyte cultures. Thus, RA, along with TGF beta and ascorbate, can now be included in the list of known Pi stimulants. All three of these factors promote mineralization in growth plate cartilage; These data support a central role for TGF beta in CPPD disease, and provide further evidence linking processes of normal and pathologic calcification in cartilage.
