Endogenous bone-resorbing factors in estrogen deficiency: cooperative effects of IL-1 and IL-6.
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-1 alpha antibody completely neutralized the bone-resorbing activity present in bone marrow supernatants from OVX mice. Antibodies against IL-1 beta, IL-6, and IL-6 receptors also neutralized it, but partially. The concentration of IL-1 alpha 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-1 beta 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-1 alpha 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Miyaura
C
C
Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
Kusano
K
K
Masuzawa
T
T
Chaki
O
O
Onoe
Y
Y
Aoyagi
M
M
Sasaki
T
T
Tamura
T
T
Koishihara
Y
Y
Ohsugi
Y
Y
D000818:Animals; D001853:Bone Marrow; D001862:Bone Resorption / Q000378:metabolism*; D015232:Dinoprostone / Q000502:physiology; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D014599:Uterus / Q000473:pathology
D004967:Estrogens; D007375:Interleukin-1; D015850:Interleukin-6; D015232:Dinoprostone