Journal article
Tristetraprolin Is Required for Alveolar Bone Homeostasis
Journal of dental research, Vol.97(8), pp.946-953
07/01/2018
DOI: 10.1177/0022034518756889
PMCID: PMC6661319
PMID: 29514008
Abstract
Tristetraprolin (TTP) is an RNA-binding protein that targets numerous immunomodulatory mRNA transcripts for degradation. Many TTP targets are key players in the pathogenesis of periodontal bone loss, including tumor necrosis factor-alpha. To better understand the extent that host immune factors play during periodontal bone loss, we assessed alveolar bone levels, inflammation and osteoclast activity in periodontal tissues, and immune response in draining cervical lymph nodes in TTP-deficient and wild-type (WT) mice in an aging study. WT and TTP-deficient (knockout [KO]) mice were used for all studies under specific pathogen-free conditions. Data were collected on mice aged 3, 6, and 9 mo. Microcomputed tomography (mu CT) was performed on maxillae where 3-dimensional images were generated and bone loss was assessed. Decalcified sections of specimens were scored for inflammation and stained with tartrate-resistant acid phosphate (TRAP) to visualize osteoclasts. Immunophenotyping was performed on single-cell suspensions isolated from primary and peripheral lymphoid tissues using flow cytometry. Results presented indicate that TTP KO mice had significantly more alveolar bone loss over time compared with WT controls. Bone loss was associated with significant increases in inflammatory cell infiltration and an increased percentage of alveolar bone surfaces apposed with TRAP+ cells. Furthermore, it was found that the draining cervical lymph nodes were significantly enlarged in TTP-deficient animals and contained a distinct pathological immune profile compared with WT controls. Finally, the oral microbiome in the TTP KO mice was significantly different with age from WT cohoused mice. The severe bone loss, inflammation, and increased osteoclast activity observed in these mice support the concept that TTP plays a critical role in the maintenance of alveolar bone homeostasis in the presence of oral commensal flora. This study suggests that TTP is required to inhibit excessive inflammatory host responses that contribute to periodontal bone loss, even in the absence of specific periodontal pathogens.
Details
- Title: Subtitle
- Tristetraprolin Is Required for Alveolar Bone Homeostasis
- Creators
- H. M. Steinkamp - Medical University of South CarolinaJ. D. Hathaway-Schrader - Medical University of South CarolinaM. B. Chavez - Medical University of South CarolinaJ. D. Aartun - Medical University of South CarolinaL. Zhang - Medical University of South CarolinaT. Jensen - Medical University of South CarolinaA. Shojaee Bakhtiari - University of South CarolinaK. L. Helke - Medical University of South CarolinaD. J. Stumpo - Medical University of South CarolinaA. V. Alekseyenko - Medical University of South CarolinaC. M. Novince - Medical University of South CarolinaP. J. Blackshear - National Institute of Environmental Health SciencesK. L. Kirkwood - University at Buffalo, State University of New York
- Resource Type
- Journal article
- Publication Details
- Journal of dental research, Vol.97(8), pp.946-953
- Publisher
- Sage
- DOI
- 10.1177/0022034518756889
- PMID
- 29514008
- PMCID
- PMC6661319
- ISSN
- 0022-0345
- eISSN
- 1544-0591
- Number of pages
- 8
- Grant note
- Intramural Program of the National Institute of Environmental Health Sciences, NIH 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) ZIAES090080 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) Genomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina K08DE025337; R01DE021423; P30GM103331; T32DE017551 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 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
- 07/01/2018
- Academic Unit
- Pediatric Dentistry
- Record Identifier
- 9984367759502771
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