Bone cell responsiveness to transforming growth factor β, parathyroid hormone, and prostaglandin E2 in normal and postmenopausal osteoporotic women

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Abstract
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-β (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-β 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. The responsiveness of bone cells from osteoporotic women to exogenous prostaglandin E2 (PGE2) was also evaluated. PGE2 (24 h) produced a dose-related biphasic effect on DNA synthesis in bone cells from both normal and osteoporotic weomen. At low concentration (10−11 M) PGE2 increased DNA synthesis whereas at higher concentration (10−7 M) it was inhibitory. cAMP production was increased by PGE2 at doses that inhibited DNA synthesis. The responsiveness to PGE2 was not different in normal bone cells and in cells from osteoporotic women with low and high DLS. These results indicate that the reduced bone cell proliferative capacity in osteoporotic postmenopausal women with low bone formation does not result from a lower than normal responsiveness to TGF-β, PTH, and PGE2.