Naslov
Fas receptor is required for estrogen deficiency-induced bone loss in mice

Autori
Kovačić, Nataša ; Grčević, Danka ; Katavić, Vedran ; Lukić, Ivan Krešimir ; Grubišić, Vladimir ; Mihovilović, Karlo ; Cvija, Hrvoje ; Croucher, Peter Ian ; Marušić, Ana

Izvornik
Laboratory investigation (0023-6837) 90 (2010), 3; 402-413

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
apoptosis; CD95; knockout mice; osteoblast; osteoclast; osteoporosis

Sažetak
Bone mass is determined by bone cell differentiation, activity, and death, which mainly occur through apoptosis. Apoptosis can be triggered by death receptor Fas (CD95), expressed on osteoblasts and osteoclasts and may be regulated by estrogen. We have previously shown that signaling through Fas inhibits osteoblast differentiation. In this study we analyzed Fas as a possible mediator of bone loss induced by estrogen withdrawal. At 4 weeks after ovariectomy (OVX), Fas gene expression was greater in osteoblasts and lower in osteoclasts in ovariectomized C57BL/6J (wild type (wt)) mice compared with sham-operated animals. OVX was unable to induce bone loss in mice with a gene knockout for Fas (Fas –/– mice). The number of osteoclasts increased in wt mice after OVX, whereas it remained unchanged in Fas –/– mice. OVX induced greater stimulation of osteoblastogenesis in Fas –/– than in wt mice, with higher expression of osteoblast-specific genes. Direct effects on bone cell differentiation and apoptosis in vivo were confirmed in vitro, in which addition of estradiol decreased Fas expression and partially abrogated the apoptotic and differentiation-inhibitory effect of Fas in osteoblast lineage cells, while having no effect on Fas-induced apoptosis in osteoclast lineage cells. In conclusion, the Fas receptor has an important role in the pathogenesis of postmenopausal osteoporosis by mediating apoptosis and inhibiting differentiation of osteoblast lineage cells. Modulation of Fas effects on bone cells may be used as a therapeutic target in the treatment of osteoresorptive disorders.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA