Bone cell responsiveness to transforming growth factor beta, parathyroid hormone, and prostaglandin E2 in normal and postmenopausal osteoporotic women.
We have shown previously that the decreased trabecular bone formation in osteoporotic postmenopausal women results from a reduced ability of osteoblastic cells to proliferate. In this study we have tested the possibility that bone cells from osteoporotic women with low bone formation have an abnormal responsiveness to hormonal or local mitogenic factors. Primary cultures of bone cells with osteoblastic characteristics were obtained by migration from the trabecular bone surface in osteoporotic postmenopausal women with high (n = 7) or low (n = 7) bone formation as evaluated histomorphometrically by the extent of double tetracycline-labeled surface (DLS). Control bone cells were obtained under identical conditions from eight normal age-matched postmenopausal women. Parameters of osteoblastic differentiation (alkaline phosphatase activity and osteocalcin production) were found to be normal and similar in bone cells from osteoporotic women with low or high DLS. In contrast, cell replication as evaluated by [3H]thymidine into DNA was 3.4-fold lower in the low DLS group compared to the high DLS group, confirming our previous findings. Treatment of quiescent bone cells with TGF-beta (0.5-1 ng/ml) for 24 h significantly stimulated DNA synthesis in osteoblastic cells from normal women and in bone cells from osteoporotic patients with low or high DLS, indicating a normal responsiveness to TGF-beta in these patients. We have compared the effect of parathyroidhormone (PTH) on bone cells from normal and osteoporotic women. Basal cAMP levels and the cAMP accumulation in response to (1-34)-hPTH were similar in bone cells from patients with low or high DLS and were not different from normal values.(ABSTRACT TRUNCATED AT 250 WORDS)
Lomri
A
A
Unité 18 INSERM, Hôpital Lariboisière, Paris, France.
Marie
P J
PJ
D000368:Aged; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D010281:Parathyroid Hormone; D016212:Transforming Growth Factor beta; D004247:DNA; D000242:Cyclic AMP; D015232:Dinoprostone