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Review
. 2012;9(9):825-32.
doi: 10.7150/ijms.5180. Epub 2012 Oct 27.

Immune regulation of osteoclast function in postmenopausal osteoporosis: a critical interdisciplinary perspective

Affiliations
Review

Immune regulation of osteoclast function in postmenopausal osteoporosis: a critical interdisciplinary perspective

Renqing Zhao. Int J Med Sci. 2012.

Abstract

Extensive studies on cross talk between immune and skeletal systems in autoimmune diseases give rise to a new discipline of 'osteoimmunology', which explores the molecular regulation of osteoclasts by immune system. Postmenopausal osteoporosis is recognized as a cytokine driven disease, but the mechanism that how estrogen deficiency interplaying with cytokines to stimulate bone loss remains to be elucidated. Although the effect of individual cytokines on osteoclast formation is well characterized, the major challenge is to fit a multitude of redundant pathways and cytokines into a systemic model of postmenopausal osteoporosis. This review presents current findings and hypothesis to explain estrogen deficiency-stimulated bone loss in a critical interdisciplinary perspective. To better understand the interaction between osteoclasts and immune system in postmenopausal osteoporosis, many of the lessons have been explored in animal models.

Keywords: cytokine; estrogen deficiency; osteoclast.; osteoimmunology.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Hematopoietic stem cell differentiation. All hematopoietic cells circulating in peripheral blood arise from pluripotent hematopoietic stem cells which differentiate into multipotent progenitors (MPPs). At the stage of multipotent progenitors (MPPs), important differentiation occurs. MPPs differentiate into the common myeloid progenitors (CMPs) and further granulocyte-macrophage progenitors (GMPs) which give rise to osteoclasts, macrophages, granulocytes and dendritic cells. MPPs also differentiate into common lymphoid progenitors (CLP) which develop into T, B and natural killer cells.
Figure 2
Figure 2
Cytokine regulation of osteoclast formation induced by estrogen deficiency. Bone loss induced by estrogen deficiency is a complex effect of a multitude of redundant pathways and cytokines working in a cooperative fashion to regulate osteoclastogenesis. Estrogen deficiency causes in a global increment in IL-7 production, especially in thymus, bone marrow and spleen. The increased production of IL-7 in bone marrow increases T cell populations and activity which increases TNF production and importation of hematogenous thymocyte progenitors into thymus. The increment of IL-7 in thymus increases the output of naïve CD4+T cell output into peripheral blood and in turn the expansion of T cell pool which increased the production of TNF. Estrogen deficiency also increases the stromal cell production of cytokines such as IL-6, IL-1, RANKL and M-CSF, that promote proliferation and differentiation of osteoclast precursors independently or cooperatively in bone marrow.

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