Sex steroids, cytokines and the bone marrow

new concepts on the pathogenesis of osteoporosis.

S. C. Manolagas, Teresita Bellido, R. L. Jilka

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Osteoclasts and osteoblasts, originating in the bone marrow from haemopoietic progenitors and mesenchymal stromal cells, respectively, are responsible for the remodelling of the skeleton throughout adult life. Upon loss of sex steroids, the production of osteoclasts in the bone marrow is increased. This is mediated by an increase in the production of interleukin 6 (IL-6), as well as an increase in the sensitivity of the osteoclastic precursors to the action of cytokines such as IL-6, owing to an up-regulation of the gp130 signal transduction pathway. Consistent with this, oestrogens as well as androgens inhibit IL-6 production through an indirect effect of their specific receptors on the transcriptional activity of the IL-6 gene promoter, and inhibit the expression of the gp130 gene. With advancing age, the ability of the marrow to maintain the high rate of osteoclastogenesis caused by the acute loss of sex steroids is diminished. This is probably the result of the negative effect of senescence on the ability of the marrow to produce stromal/osteoblastic cells, which provide the essential support for osteoclastogenesis. These observations suggest that inappropriate production of osteoclasts or inadequate production of osteoblasts in the bone marrow are fundamental cellular changes in the pathogenesis of postmenopausal and senescence-associated osteoporosis, respectively.

Original languageEnglish (US)
JournalCIBA Foundation Symposia
Volume191
StatePublished - 1995
Externally publishedYes

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Osteoporosis
Bone Marrow
Steroids
Cytokines
Interleukin-6
Osteoclasts
Osteoblasts
Osteogenesis
Stromal Cells
Mesenchymal Stromal Cells
Skeleton
Androgens
Signal Transduction
Estrogens
Up-Regulation
Gene Expression
Genes

ASJC Scopus subject areas

  • General

Cite this

Sex steroids, cytokines and the bone marrow : new concepts on the pathogenesis of osteoporosis. / Manolagas, S. C.; Bellido, Teresita; Jilka, R. L.

In: CIBA Foundation Symposia, Vol. 191, 1995.

Research output: Contribution to journalArticle

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