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Butyrate Inhibits Osteoclast Activity In Vitro and Regulates Systemic Inflammation and Bone Healing in a Murine Osteotomy Model Compared to Antibiotic-Treated Mice.
- Source :
-
Mediators of inflammation [Mediators Inflamm] 2021 Dec 10; Vol. 2021, pp. 8817421. Date of Electronic Publication: 2021 Dec 10 (Print Publication: 2021). - Publication Year :
- 2021
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Abstract
- Short-chain fatty acids (SCFAs) produced by the gut microbiota have previously been demonstrated to play a role in numerous chronic inflammatory diseases and to be key mediators in the gut-bone signaling axis. However, the role of SCFAs in bone fracture healing and its impact on systemic inflammation during the regeneration process has not been extensively investigated yet. The aim of this study was to first determine the effects of the SCFA butyrate on key cells involved in fracture healing in vitro , namely, osteoclasts and mesenchymal stromal cells (MSCs), and second, to assess if butyrate supplementation or antibiotic therapy impacts bone healing, systemic immune status, and inflammation levels in a murine osteotomy model. Butyrate significantly reduced osteoclast formation and resorption activity in a dose-dependent manner and displayed a trend for increased calcium deposits in MSC cultures. Numerous genes associated with osteoclast differentiation were differentially expressed in osteoclast precursor cells upon butyrate exposure. In vivo , antibiotic-treated mice showed reduced SCFA levels in the cecum, as well as a distinct gut microbiome composition. Furthermore, circulating proinflammatory TNF α , IL-17a, and IL-17f levels, and bone preserving osteoprotegerin (OPG), were increased in antibiotic-treated mice compared to controls. Antibiotic-treated mice also displayed a trend towards delayed bone healing as revealed by reduced mineral apposition at the defect site and higher circulating levels of the bone turnover marker PINP. Butyrate supplementation resulted in a lower abundance of monocyte/macrophages in the bone marrow, as well as reduced circulating proinflammatory IL-6 levels compared to antibiotic- and control-treated mice. In conclusion, this study supports our hypothesis that SCFAs, in particular butyrate, are important contributors to successful bone healing by modulating key cells involved in fracture healing as well as systemic inflammation and immune responses.<br />Competing Interests: All authors declare that they have no conflicts of interest.<br /> (Copyright © 2021 Alexandra Wallimann et al.)
- Subjects :
- Animals
Cell Differentiation drug effects
Cells, Cultured
Cytokines analysis
Fatty Acids, Volatile pharmacology
Fracture Healing physiology
Gastrointestinal Microbiome drug effects
Humans
Inflammation Mediators analysis
Levofloxacin pharmacology
Male
Mice
Mice, Inbred C57BL
Osteoclasts cytology
Osteotomy
Rifampin pharmacology
Anti-Bacterial Agents pharmacology
Butyrates pharmacology
Fracture Healing drug effects
Inflammation etiology
Osteoclasts drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1466-1861
- Volume :
- 2021
- Database :
- MEDLINE
- Journal :
- Mediators of inflammation
- Publication Type :
- Academic Journal
- Accession number :
- 34924815
- Full Text :
- https://doi.org/10.1155/2021/8817421