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Murine Bone Exhibits Temporal Response to Metabolic Acidosis

2022; RELX Group (Netherlands); Linguagem: Inglês

10.2139/ssrn.4111775

1556-5068

Anna K. Peterson, Mikayla Moody, Brian Wingender, Katya Morozov, Iris Nakashima, Margaret Easson, Ron Ben Abraham, Tannin A. Schmidt, Leslie A. Caromile, Alix Deymier,

Diet and metabolism studies

Download This Paper Open PDF in Browser Add Paper to My Library Share: Permalink Using these links will ensure access to this page indefinitely Copy URL Murine Bone Exhibits Temporal Response to Metabolic Acidosis BONE-D-22-00390 21 Pages Posted: 17 May 2022 See all articles by Anna PetersonAnna PetersonUniversity of Connecticut Health Center - Dept of Biomedical EngineeringMikayla MoodyUniversity of Connecticut Health Center - Dept of Biomedical EngineeringBrian WingenderUniversity of Connecticut Health Center - Dept of Biomedical EngineeringKatya MorozovUniversity of Connecticut Health Center - Dept of Biomedical EngineeringIris NakashimaUniversity of Connecticut Health Center - Dept of Biomedical EngineeringMargaret EassonUniversity of Connecticut Health Center - Dept of Biomedical EngineeringRon AbrahamUniversity of Connecticut Health Center - Dept of Biomedical EngineeringTannin A. SchmidtUniversity of Connecticut Health Center - Dept of Biomedical EngineeringLeslie CaromileUniversity of Connecticut - School of MedicineAlix DeymierUniversity of Connecticut - Department of Biomedical Engineering Abstract Metabolic acidosis (MA), a disease affecting millions annually, is clinically characterized by a decrease in systemic pH and bicarbonate (HCO3-). MA has been shown to have skeletal consequences such as increased bone loss and fractures as a result of cellular resorption and physiochemical dissolution. We characterized the skeletal phenotypes resulting from two independent regimes of ammonium chloride acid-dosing in skeletally mature mice for 1, 3, 7, and 14 days to establish the temporal progression of skeletal defects. The classical, flat-dose model resulted in a temporary decrease in blood pH but did not reduce blood bicarbonate levels. Minimal alterations were observed in bone composition, structure, mechanics, and cellular behavior. However, graded administration of NH4Cl with increased dosing as a function of time maintained MA for up to 14 days. This resulted in decreased bone mineral content, collagen organization, and bone volume while increasing mineral crystallinity at early time points followed by a return to baseline. Despite significant changes in bone tissue quality, there was no change observed in osteoclast number, activity, or bone formation rate at any time in response to acidosis, suggesting that physiochemical processes are primarily responsible for the compromised bone. Changes to the matrix lead to a decrease in bone toughness at early time points, which may explain the increased fracture risk seen in vivo. Ultimately, we conclude that the bone phenotype resultant of MA in mice is influenced by both duration and dosing of exogenous acid loading. Note: Funding Information: Research funding was provided by Prof Deymier’s Startup Funds at UConn Health and NSF CAREER grant 2044870. Ron Abraham was funded in part by the Health Research program. Mikayla Moody was funded in part by the GEM Fellowship and Harriott Fellowship. Anna Peterson and Iris Nakashima were funded in part by fellowships from the UCHC Graduate School. Declaration of Interests: None. Ethics Approval Statement: All animal experimental procedures were approved by the Institutional Animal Care and Use Committee at UConn Health Center and Columbia University, and comply with the National Institutes of Health guide for the care and use of laboratory animals (NIH Publications No. 8023, revised 1978). Keywords: Acidosis, Bone remodeling, Biomechanics, Bone composition, Bone structure Suggested Citation: Suggested Citation Peterson, Anna and Moody, Mikayla and Wingender, Brian and Morozov, Katya and Nakashima, Iris and Easson, Margaret and Abraham, Ron and Schmidt, Tannin A. and Caromile, Leslie and Deymier, Alix, Murine Bone Exhibits Temporal Response to Metabolic Acidosis. BONE-D-22-00390, Available at SSRN: https://ssrn.com/abstract=4111775 Anna Peterson University of Connecticut Health Center - Dept of Biomedical Engineering ( email ) Mikayla Moody University of Connecticut Health Center - Dept of Biomedical Engineering ( email ) United States Brian Wingender University of Connecticut Health Center - Dept of Biomedical Engineering ( email ) Katya Morozov University of Connecticut Health Center - Dept of Biomedical Engineering ( email ) Iris Nakashima University of Connecticut Health Center - Dept of Biomedical Engineering ( email ) Margaret Easson University of Connecticut Health Center - Dept of Biomedical Engineering ( email ) Ron Abraham University of Connecticut Health Center - Dept of Biomedical Engineering ( email ) Tannin A. Schmidt University of Connecticut Health Center - Dept of Biomedical Engineering ( email ) United States Leslie Caromile University of Connecticut - School of Medicine ( email ) Alix Deymier (Contact Author) University of Connecticut - Department of Biomedical Engineering Farmington, CTUnited States Download This Paper Open PDF in Browser Do you want regular updates from SSRN on Twitter? Follow SSRN Paper statistics Downloads 5 Abstract Views 8 PlumX Metrics Related eJournals Rheumatology & Orthopedics eJournal Follow Rheumatology & Orthopedics eJournal Subscribe to this fee journal for more curated articles on this topic FOLLOWERS 42 PAPERS 627 Feedback Feedback to SSRN Feedback (required) Email (required) Submit If you need immediate assistance, call 877-SSRNHelp (877 777 6435) in the United States, or +1 212 448 2500 outside of the United States, 8:30AM to 6:00PM U.S. Eastern, Monday - Friday. 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