Increased osteoclast development after estrogen loss:​ mediation by interleukin-6

Jilka, Robert L.; Hangoc, Giao; Girasole, Giuseppe; Passeri, Giovanni; Williams, Daniel C.; Abrams, John S.; Boyce, Brendan; Broxmeyer, Hal; Manolagas, Stavros C.

Affiliations

¹Section of Endocrinology and Metabolism, Department of Veterans Affairs Medical Center, and the Departments of Medicine and Biochemistry, Indiana University School of Medicine, Indianapolis, IN 46202

²Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202

³Lilly Research Laboratories, Indianapolis, IN 46285

⁴DNAX Research Institute for Cellular and Molecular Biology, Palo Alto, CA 94304

⁵Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78284

Abstract

Osteoclasts, the cells that resorb bone, develop from hematopoietic precursors of the bone marrow under the control of factors produced in their microenvironment. The cytokine interleukin-6 can promote hematopoiesis and osteoclastogenesis. Interleukin-6 production by bone and marrow stromal cells is suppressed by 17β-estradiol in vitro. In mice, estrogen loss (ovariectomy) increased the number of colony-forming units for granulocytes and macrophages, enhanced osteoclast development in ex vivo cultures of marrow, and increased the number of osteoclasts in trabecular bone. These changes were prevented by 17β-estradiol or an antibody to interleukin-6. Thus, estrogen loss results in an interleukin-6-mediated stimulation of osteoclastogenesis, which suggests a mechanism for the increased bone resorption in postmenopausal osteoporosis.

Links

DOI: 10.1126/science.1621100

PubMed: 1621100

WoS: A1992JC16500036

JSTOR: 2877439

History

Received: 1992-02-19

Accepted: 1992-05-11

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