ECTS2013 Poster Presentations Cell biology: osteoblasts and bone formation (50 abstracts)
Regulation and function of immunosuppressive molecule human leukocyte antigen G5 in human bone tissue
Frederic Deschaseaux 1 , Julien Gaillard 2, , Alain Langonné 2 , Christophe Chauveau 4 , Abderrahim Naji 5 , Amina Bouacida 1, , Philippe Rosset 6 , Dominique Heymann 7 , Gonzague de Pinieux 6 , Nathalie Rouas-Freiss 5 & Luc Sensébé 1
Bone-marrow mesenchymal stem cells (MSCs) are the origin of bone-forming cells with immunomodulation potential. Among the generated immunosuppressive molecules there is HLA-G5. HLA-G proteins play a crucial role in promoting the acceptance of allografts. However, the mechanisms regulating the expression of HLA-G5 in human MSCs are unknown. We induced differentiation of human MSCs (harvested from iliac crests of healthy volunteers after their informed consent following approved Ethical Local Committee of Tours Hospital) and found that HLA-G5 was greatly upregulated only in osteoblastic cells (+63% for mRNA). Growth plates and bone callus post-fracture in adults showed that only bone lining cells and mesenchymal progenitors were positive for HLA-G5. Use of gene silencing and dominant-negative factors revealed that HLA-G5 depends on the expression and function of the skeletogenesis master genes RUNX2 and DLX5. In addition, HLA-G5 could directly inhibit osteoclastogenesis by acting on monocytes through SHP1. However, in mature osteoblasts, the expression of HLA-G5 protein was greatly suppressed (above 100% suppression) whereas the pro-osteoclastogenic factor, RANKL, was concomitantly increased. Downregulation of HLA-G5 expression during the maturation of osteoblasts was due to binding of the repressor GLI3, a signal transducer of the Hedgehog pathway, to the GLI binding element within the HLA-G promoter. Our findings show that bone tissue specifically expresses HLA-G5, with a key role in bone homeostasis.
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Bone Abstracts
ISSN 2052-1219 (online)
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