AI Article Synopsis

  • Fas ligand (FasL) plays a role in programmed cell death and immune responses, and recent research suggests it may also influence bone health by inducing death in osteoclasts, which are cells that break down bone.
  • The study focuses on the effect of FasL on osteocytes, the primary cell type in mature bone, finding that FasL stimulation significantly downregulates sclerostin, a key marker and negative regulator of bone formation, alongside other important osteogenic markers.
  • The results indicate that FasL's impact on osteocytes occurs via caspase-independent mechanisms, enhancing our understanding of the diverse functions of Fas/FasL signaling in bone biology.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389703PMC
http://dx.doi.org/10.3390/biology10080757DOI Listing

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