Bilirubin as an inhibitor of cartilage metabolism: effect on avian chondrocyte proliferation in cell culture.
Elevated levels of bilirubin and other tetrapyrroles are common to a number of chronic hematologic and liver diseases that can result in growth failure. This report establishes a cellular model system for the study of these endogenous growth inhibitors. Primary chondrocyte cultures were prepared from embryonic chick cartilage; cells were incubated (0.3 X 10(5) cells per plate) in tissue culture medium containing 10% fetal bovine serum (FBS) with or without added bilirubin, 0.01-0.10 mM. Bilirubin caused profound, dose-dependent inhibition of chondrocyte proliferation: after 7 days, control incubations contained 11.45 +/- 2.0 X 10(5) cells per plate versus 4.92 +/- 0.55 X 10(5) cells per plate for wells with added 0.01 mM bilirubin and 1.76 +/- 0.30 X 10(5) for cultures with added 0.05 mM bilirubin. In chondrocytes cultured for 3 days, the addition of 0.05 mM bilirubin was associated with inhibition of [3H]thymidine incorporation into DNA (47 +/- 5% of control), [3H]uridine incorporation into RNA (11 +/- 0.05% of control), and [14C]leucine incorporation into proteins (16 +/- 1% of control). The inhibition of chondrocyte proliferation induced by a range of bilirubin concentrations (0.01-0.10 mM) was in no way attenuated by the addition of physiologic concentrations of albumin (4 g/dl). After 3 days in media containing bilirubin or heme (at equimolar concentrations), chondrocytes were subsequently incubated in FBS alone for an additional 3 days; only partial reversal of the bilirubin (or heme)-induced inhibition was then observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medical Specialties, University of Texas M.D. Anderson Cancer Center, Houston.
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Vassilopoulou-Sellin
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Rey-Bear
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Oyedeji
D000818:Animals; D001663:Bilirubin / Q000502:physiology*; D002356:Cartilage / Q000166:cytology / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D006418:Heme / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D012710:Serum Albumin, Bovine; D006418:Heme; D001663:Bilirubin