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Endogenous bone‐resorbing factors in estrogen deficiency: Cooperative effects of IL‐1 and IL‐6
Author(s) -
Miyaura Chisato,
Kusano Kenichiro,
Masuzawa Toshihide,
Chaki Osamu,
Onoe Yoshiko,
Aoyagi Maki,
Sasaki Takahisa,
Tamura Tatsuya,
Koishihara Yasuo,
Ohsugi Yoshiyuki,
Suda Tatsuo
Publication year - 1995
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650100914
Subject(s) - endocrinology , bone resorption , bone marrow , ovariectomized rat , medicine , resorption , endogeny , chemistry , bone remodeling , osteoporosis , estrogen
Estrogen deficiency causes a marked bone loss by stimulating osteoclastic bone resorption. To explore the endogenous bone‐resorbing factors involved in estrogen deficiency, we examined the bone‐resorbing activity present in the supernatant fraction of mouse bone marrow collected from ovariectomized (OVX) mice. Adding bone marrow supernatants at 20–80% to organ cultures of mouse long bones dose‐dependently stimulated bone resorption. The endogenous bone‐resorbing activity present in bone marrow supernatants from OVX mice was much higher than that from sham‐operated mice 2–4 weeks after surgery, and it was significantly diminished by indomethacin in vitro. Anti‐IL‐1α antibody completely neutralized the bone‐resorbing activity present in bone marrow supernatants from OVX mice. Antibodies against IL‐1β, IL‐6, and IL‐6 receptors also neutralized it, but partially. The concentration of IL‐1α measured by ELISA was much higher in bone marrow supernatants than in sera, but it was not appreciably changed before or after OVX. The concentration of IL‐1β in bone marrow supernatants from OVX mice was less than the detection limit. OVX stimulated IL‐1 activity in bone marrow supernatants measured by means of the proliferation of thymocytes. However, the level of IL‐1α present in bone marrow supernatants from OVX mice was insufficient to stimulate bone resorption. Compared with the serum concentration, bone marrow supernatants contained a much higher level of IL‐6 as well, and it was further increased by OVX. However, IL‐6 alone present in bone marrow supernatants from OVX mice again did not stimulate bone resorption. The concurrent addition of IL‐1 (50 pg/ml), IL‐6 (0.2 ng/ml), sIL‐6 receptor (1 ng/ml), and PGE 2 (7 ng/ml), which equaled the endogenous concentrations in bone marrow supernatants from OVX mice, co‐operatively induced bone resorption. These results suggest that the enhanced bone resorption that occurs during estrogen deficiency is due to multi‐factors rather than to a single factor.