engleski

Bone Phenotype of the Fas Ligand Knockour Mice

Fas/Fas ligand (FasL) system is an apoptotic pathway primarily involved in the T-lymphocyte homeostasis, but also in bone mass regulation. We have previously shown that increased bone mass is a part of the phenotype of the female mice with mutation in FasL (gld mice). As immunoproliferative and bone phenotypes of gld mice are variable, we used mice with a FasL knockout (FasL -/-) to study the role of FasL in bone homeostasis. We first analyzed basic bone phenotype of twelve week-old male and female wild-type and FasL -/- mice (n=8). Femoral sections were used for standard histomorphometry, whereas tibiae and tibial bone marrow were used as a source of osteoblast and osteoclast progenitors for cell culture. Histomorphometry revealed that male FasL -/- mice had less osteoclasts on bone surfaces(6.34 (SD=1.40) in wild-type mice vs. 4.32 (SD=1.23) in FasL -/-, p=0.01), but similar percent trabecular volume (BV/TV), trabecular thickness (Tb.Th.), trabecular separation (Tb.Sp.), and trabecular number (Tb.No.) as their wild-type controls. Female FasL -/- mice had similar number of osteoclasts (6.05 (SD=1.29) in wild-type mice vs. 5.39 (SD=1.61) in FasL -/-, p=0.19) on bone surfaces, decreased Tb.Sp., and increased Tb.No. compared to wild-type controls. Both male and female FasL -/- mice had increased osteoblastogenesis and decreased osteoclastogenesis in vitro. Our results indicate that complete absence of FasL still mildly affects bone, as in gld mice. As the bone phenotype differed in male and female mice, our future experiments will focus on studying the role of estrogen in FasL-/- bone phenotype.

fas ligand ; bone phenotype ; apoptosis

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