RT Journal Article
SR Electronic
T1 Specific targeting of inflammatory osteoclastogenesis by the probiotic yeast <em>S. boulardii</em> CNCM I-745 reduces bone loss in osteoporosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.08.01.502322
DO 10.1101/2022.08.01.502322
A1 Maria-Bernadette Madel
A1 Julia Halper
A1 Lidia Ibáñez
A1 Claire Lozano
A1 Matthieu Rouleau
A1 Antoine Boutin
A1 Rodolphe Pontier-Bres
A1 Thomas Ciucci
A1 Majlinda Topi
A1 Christophe Hue
A1 Jérôme Amiaud
A1 Salvador Iborra
A1 David Sancho
A1 Dominique Heymann
A1 Henri-Jean Garchon
A1 Dorota Czerucka
A1 Florence Apparailly
A1 Isabelle Duroux-Richard
A1 Abdelilah Wakkach
A1 Claudine Blin-Wakkach
YR 2022
UL http://biorxiv.org/content/early/2022/08/03/2022.08.01.502322.abstract
AB Bone destruction is a hallmark of chronic inflammation, and bone-resorbing osteoclasts arising under such a condition differ from steady-state ones. However, osteoclast diversity remains poorly explored. Here, we combined transcriptomic profiling, differentiation assays and in vivo analysis in mouse to decipher specific traits for inflammatory and steady state osteoclasts. We identified and validated the pattern-recognition receptors (PRR) TLR2, Dectin-1 and Mincle, all involved in yeast recognition as major regulators of inflammatory osteoclasts. We showed that administration of the yeast probiotic Saccharomyces boulardi CNCM I-745 (Sb) in vivo reduced bone loss in OVX but not sham mice by reducing inflammatory osteoclasts. This beneficial impact of Sb is mediated by the regulation of the inflammatory environment required for the generation of inflammatory osteoclasts. We also showed that Sb derivatives as well as agonists of TLR2, Dectin-1 and Mincle specifically inhibited directly the differentiation of inflammatory but not steady state osteoclasts in vitro. These findings demonstrate a preferential use of the PRR-associated costimulatory differentiation pathway by inflammatory osteoclasts, thus enabling their specific inhibition, which opens new therapeutic perspectives for inflammatory bone loss.Competing Interest StatementC.B-W. and D.C received a research grant from Biocodex. Biocodex had no role in the design of the study, in the analysis and interpretation of the data and in the preparation of the manuscript. All other authors declare no conflict of interest.