Journal article
Commensal Gut Microbiota Immunomodulatory Actions in Bone Marrow and Liver have Catabolic Effects on Skeletal Homeostasis in Health
Scientific reports, Vol.7(1), 5747
07/18/2017
DOI: 10.1038/s41598-017-06126-x
PMCID: PMC5515851
PMID: 28720797
Abstract
Despite knowledge the gut microbiota regulates bone mass, mechanisms governing the normal gut microbiota's osteoimmunomodulatory effects on skeletal remodeling and homeostasis are unclear in the healthy adult skeleton. Young adult specific-pathogen-free and germ-free mice were used to delineate the commensal microbiota's immunoregulatory effects on osteoblastogenesis, osteoclastogenesis, marrow T-cell hematopoiesis, and extra-skeletal endocrine organ function. We report the commensal microbiota has anti-anabolic effects suppressing osteoblastogenesis and pro-catabolic effects enhancing osteoclastogenesis, which drive bone loss in health. Suppression of Sp7(Osterix) and Igf1 in bone, and serum IGF1, in specific-pathogen-free mice suggest the commensal microbiota's anti-osteoblastic actions are mediated via local disruption of IGF1-signaling. Differences in the RANKL/OPG Axis in vivo, and RANKL-induced maturation of osteoclast-precursors in vitro, indicate the commensal microbiota induces sustained changes in RANKL-mediated osteoclastogenesis. Candidate mechanisms mediating commensal microbiota's pro-osteoclastic actions include altered marrow effector CD4(+) T-cells and a novel Gut-Liver-Bone Axis. The previously unidentified Gut-LiverBone Axis intriguingly implies the normal gut microbiota's osteoimmunomodulatory actions are partly mediated via immunostimulatory effects in the liver. The molecular underpinnings defining commensal gut microbiota immunomodulatory actions on physiologic bone remodeling are highly relevant in advancing the understanding of normal osteoimmunological processes, having implications for the prevention of skeletal deterioration in health and disease.
Details
- Title: Subtitle
- Commensal Gut Microbiota Immunomodulatory Actions in Bone Marrow and Liver have Catabolic Effects on Skeletal Homeostasis in Health
- Creators
- Chad M. Novince - Medical University of South CarolinaCarolyn R. Whittow - Medical University of South CarolinaJohannes D. Aartun - Medical University of South CarolinaJessica D. Hathaway - Medical University of South CarolinaNicole Poulides - Medical University of South CarolinaMichael B. Chavez - Medical University of South CarolinaHeidi M. Steinkamp - Medical University of South CarolinaKaeleigh A. Kirkwood - Medical University of South CarolinaEmily Huang - Medical University of South CarolinaCaroline Westwater - Medical University of South CarolinaKeith L. Kirkwood - Medical University of South Carolina
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.7(1), 5747
- DOI
- 10.1038/s41598-017-06126-x
- PMID
- 28720797
- PMCID
- PMC5515851
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Springer Nature
- Number of pages
- 18
- Grant note
- UL1TR000062 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) K08DE025337; R01DE021423; P30GM103331; T32DE017551; R25DE022677; UL1TR000062 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30GM103331 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) T32DE017551 / NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR)
- Language
- English
- Date published
- 07/18/2017
- Academic Unit
- Pediatric Dentistry
- Record Identifier
- 9984367651202771
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