MHC Class II Transactivator Is an In Vivo Regulator of Osteoclast Differentiation and Bone Homeostasis Co-opted From Adaptive Immunity
Elisa Benasciutti, Elisabetta Mariani, Laura Oliva, Maria Scolari, Egon Perilli, Emmanuele Barras, Enrico Milan, Ugo Orfanelli, Nicola L Fazzalari, Lara Campana, Annalisa Capobianco, Luc Otten, Francesca Particelli, Hans Acha-Orbea, Fabio Baruffaldi, Roberta Faccio, Roberto Sitia, Walter Reith, Simone Cenci
JOURNAL OF BONE AND MINERAL RESEARCH | WILEY | Published : 2014
The molecular networks controlling bone homeostasis are not fully understood. The common evolution of bone and adaptive immunity encourages the investigation of shared regulatory circuits. MHC Class II Transactivator (CIITA) is a master transcriptional co-activator believed to be exclusively dedicated for antigen presentation. CIITA is expressed in osteoclast precursors, and its expression is accentuated in osteoporotic mice. We thus asked whether CIITA plays a role in bone biology. To this aim, we fully characterized the bone phenotype of two mouse models of CIITA overexpression, respectively systemic and restricted to the monocyte-osteoclast lineage. Both CIITA-overexpressing mouse models ..View full abstract
Awarded by Ministero della Salute, Giovani Ricercatori
Awarded by Italian Association for Cancer Research
This study was supported by research grants to SC (European Calcified Tissue Society 2009 Career Establishment Award; Ministero della Salute, Giovani Ricercatori 2008-1143560 and 2009-1607545; Multiple Myeloma Research Foundation, 2010 Senior Research Award; and the Italian Association for Cancer Research, Special Program Molecular Clinical Oncology 5 per mille 9965). Work in WR's lab was supported by the Swiss National Science Foundation, the National Center of Competence in Research on Neural Plasticity and Repair (NCCR-NEURO), the Swiss Multiple Sclerosis Society, and the Geneva Cancer League. We are indebted to M Ascagni, M Baleani, C Covino, C Cucchi, A Del Fattore, S Dell'Oro, C Fersini, D Finke, F Grassi, N Lo Iacono, R Pacifici, MC Panzeri, N Pengo, P Podini, M Rocchi, P Rovere-Querini, N Rucci, C Sobacchi, S Takeshita, A Teti, A Villa, K Weilbaecher, and A Zallone for reagents and scientific advice. We are thankful to R Brambati, A Fella, and F Loro for technical and administrative assistance.