It was reported earlier that IL-1 production by cultured monocytes and the ratio of helper (CD4) to suppressor (CD8) lymphocytes in peripheral blood are different in osteoporotic compared to nonosteoporotic subjects. We examined these and several other parameters related to the biosynthetic activity and differentiation status of peripheral blood mononuclear cells (PBMC) in untreated osteoporotic postmenopausal women (age 65 +/- 7, n = 46), nonosteoporotic postmenopausal women (age 55 +/- 3, n = 20), and nonosteoporotic premenopausal women (age 37 +/- 7, n = 8), as defined by spine density. We found that unstimulated monocytes from osteoporotics did not produce detectable IL-1 beta as determined by ELISA. In addition, there were no significant differences between osteoporotics and nonosteoporotics in IL-1 beta or IFN-gamma production by PBMC stimulated with OKT3, a monoclonal antibody to the T cell-receptor complex. The proliferative response of lymphocytes to OKT3 was significantly less (p < 0.02) in osteoporotics compared to nonosteoporotic post- and premenopausal women; multiple-regression analysis, however, indicated that this difference was not due to bone density but to age. Flow cytometric analysis of PBMC revealed no difference between osteoporotics and nonosteoporotics in the distribution of 18 phenotypic subsets determined, including CD4- or CD8-positive lymphocytes or the ratio of CD4 to CD8 cells. Further, there was no correlation of the surface markers with bone density, the exceptions being the subsets expressing the CD3/CD56 and CD8/CD56 markers, which were inversely related to spine density in the osteoporotic women.(ABSTRACT TRUNCATED AT 250 WORDS)
Bone changes and aortic calcification were compared radiographically for different age groups of the inhabitants of two communities on the Kii Peninsula at the central southern tip of the Japanese mainland, one a mountainous Shichikawa village with a traditionally restricted nutritional intake and the other a seacoast village on Oshima Island with an abundant nutritional supply. Changes in the physical properties of the bone were also assessed by resonance measurement. In the mountainous village, bone loss appeared to occur more rapidly than in the seacoast village, as indicated by a significantly higher frequency of thoracic vertebral deformity and more pronounced age-bound decrease of ulnar resonant frequency. Aortic calcification was also more frequent in Shichikawa than on Oshima Island. Such differences were more evident in women than in men. The poorer nutritional intake (especially of calcium and vitamin D) of persons living in the mountainous village (which receives less sunshine) might be responsible for the accelerated age-bound degenerative changes observed in their skeletal and vascular systems.
It was recently shown that interleukin-6 (IL-6) is produced by bone and bone marrow-derived stromal cells and that it plays an important role in osteoclast development. Here we examined whether parathyroid hormone (PTH), calcitonin (CT), or the calcitonin gene-related peptide (CGRP) influence IL-6 production by two murine bone marrow-derived stromal cell lines: the preadipocyte-like stromal cell line +/+ LDA11 and the fibroendothelial stromal cell line MBA 13.2. We found that CGRP (but not PTH or CT) exerted a dose-dependent increase in cAMP and IL-6 production in the +/+ LDA11 cells. In addition, CGRP had an inhibiting effect on the proliferation of this stromal cell line. CGRP, however, did not affect cAMP or IL-6 in the rat osteogenic sarcoma cell line UMR-106-06, which exhibits CT receptors, whereas CT stimulated both cAMP and IL-6 by the UMR-106-01 cells. In contrast to the specificity of the IL-6 response of the +/+ LDA11 cells to CGRP, IL-6 production by the MBA 13.2 stromal cells was stimulated by PTH whereas CGRP or CT had no effect. These data suggest that bone marrow-derived stromal cells express receptors for either CGRP or PTH in a phenotype-specific manner and that, acting via these receptors, CGRP and PTH stimulate IL-6 production by stromal cells. In addition, the evidence for specific receptors for the neuropeptide CGRP in bone marrow stromal cells and an effect of CGRP on IL-6 raises the possibility for a role of cytokines in a putative interplay between neuronal stimuli and bone.
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