During bone development, FasL acts not only through the traditional apoptotic mechanism regulating the amount of bone-resorbing osteoclasts, but there is also growing evidence about its effect on cell differentiation. Expression of osteoblastic factors was followed in non differentiated and differentiating primary calvarial cells obtained from FasL-deficient (gld) mice. The gld cells showed decreased expression of the key osteoblastic molecules osteocalcin (Ocn), osteopontin (Opn), and alkaline phosphatase (Alpl) in both groups. Notably, receptor activator of nuclear factor kappa-B ligand (Rankl) was unchanged in non-differentiated gld vs. wild type (wt) cells but decreased in differentiating gld cells. Osteoprotegerin (Opg) in the gld samples was increased in both groups. Opg vs. Rankl expression levels favored Opg in the case of non-differentiated cells but Rankl in differentiating ones. These results expand information on the involvement of FasL in non-apoptotic cell pathways related to osteoblastogenesis and consequently also osteoclastogenesis and pathologies such as osteoporosis.

• MeSH
• buněčná diferenciace MeSH
• glykoproteiny * metabolismus   MeSH
• kosti a kostní tkáň metabolismus   MeSH
• myši MeSH
• osteoblasty MeSH
• osteogeneze * MeSH
• osteoklasty metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glykoproteiny * MeSH

AIM: Fas ligand (FasL) belongs to the tumour necrosis factor superfamily regulating bone turnover, inflammation, and apoptosis. The appendicular and axial skeleton phenotype of mature Faslgld mice has been reported. The impact of FasL on the alveolar bone providing support for the teeth at mature stages under healthy and induced inflammatory conditions remains unknown. MATERIALS AND METHODS: We performed a phenotypical analysis of mice carrying the homozygous Faslgld mutation and wild-type (WT) mice (C57BL/6) under healthy conditions and upon ligature-induced periodontitis. After 12 days, micro-computed tomography analysis revealed the distance between the cement enamel junction and the alveolar bone crest. Additional structural parameters, such as the bone volume fraction (BV/TV) and the periodontal ligament space volume, were measured. Histological analyses were performed to visualize the catabolic changes at the defect site. RESULTS: Healthy Faslgld mice were found to have more periodontal bone than their WT littermates. Faslgld had no significant effect on inflammatory osteolysis compared to WT controls with ligatures. Histology revealed eroded surfaces at the root and in the inter-proximal bone in both strains. CONCLUSIONS: Our findings suggest that FasL is a catabolic factor in alveolar bone homeostasis but it does not affect the inflammatory osteolysis.

• Klíčová slova
• FasL, gld, ligature, osteolysis, periodontitis,
• MeSH
• homeostáza MeSH
• ligand Fas MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• osteolýza * MeSH
• rentgenová mikrotomografie MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ligand Fas MeSH

The Fas ligand (FasL) is known from programmed cell death, the immune system, and recently also from bone homeostasis. As such, Fas signalling is a potential target of anti-osteoporotic treatment based on the induction of osteoclastic cell death. Less attention has been paid to osteocytes, although they represent the majority of cells within the mature bone and are the key regulators. To determine the impact of FasL stimulation on osteocytes, differentiated IDG-SW3 cells were challenged by FasL, and their osteogenic expression profiles were evaluated by a pre-designed PCR array. Notably, the most downregulated gene was the one for sclerostin, which is the major marker of osteocytes and a negative regulator of bone formation. FasL stimulation also led to significant changes (over 10-fold) in the expression of other osteogenic markers: Gdf10, Gli1, Ihh, Mmp10, and Phex. To determine whether these alterations involved caspase-dependent or caspase-independent mechanisms, the IDG-SW3 cells were stimulated by FasL with and without a caspase inhibitor: Q-VD-OPh. The alterations were also detected in the samples treated by FasL along with Q-VD-OPh, pointing to the caspase-independent impact of FasL stimulation. These results contribute to an understanding of the recently emerging pleiotropic effects of Fas/FasL signalling and specify its functions in bone cells.

• Klíčová slova
• Fas/FasL signalling, bone, caspases, non-apoptotic, osteocyte differentiation,
• Publikační typ
• časopisecké články MeSH