engleski

Mice with Fas ligand (gld) mutation form more bone after bone marrow ablation than wild-type controls

Among other immune cells within the bone marrow microenvironment, T-lymphocytes may be involved in the maintatinence of normal bone homeostasis via the production of cytokines and direct cell to cell interaction. One of the pathways involved in intercellular ineractions is the Fas recepto-Fass-L system, which acts as an apoptotic pathway. Activated T lymphocates within bone -bone marrow microenvironment express FasL, whereas Fas is expressed on many other cells including osteoblasts. We studied the role of the Fas system in bione formation using a previously described model for bone marrow ablation. Twelve week-old male C57BL/6 mice (wild-type) and mice with the FasL mutation (gld/gld) of the same genetic background were sacrificed at 6, 8, and 10 days after mechanical ablation of tibial bone marrow. Tibiae were processed for histology and biochemical analysis and total tibial RNA was extracted for Northern-blot analysis. Histomorphometric analisys showed that gld/gld mice had greater trabecular area (Tb.Ar.), trabecular perimeter (Tb.Pm.), trabecular number per milimeter (Tb.No./mm) and trabecular bone volume/total bone volume (Tb.BV/TV) and smaller trabecular separation (Tb.Sp.) than wild-type controls at 6 postablation days. The differnce in Tb.BV/TV was still evident at 8 postablation days, as well as increased trabecular width (Tb.Wi.) in gld/gld mice. At 10 postablation days, there was no difference in histomorphometric parameters, but Northern abnalysis of bone-related markers showed higher expression of bone sialoprotein, osteocalcin, collagen, and osteopontin mRNA in gld/gld mice than in wild-type controls. Although alkaline phosphatase activity was higher in gld/gld mice than in wild-type controls at all time pooints the difference never reached statistical significance. Our data suggersts that FasL is an impoortant regulator of new bone formation, possibly through its regulation of osteoblast apoptosis.

lymphocytes; bone marrow; osteoresorption; cytokines; cell differentiation

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