Impact of the Microbiome on Osteoimmunology and Skeletal Development

微生物组对骨免疫学和骨骼发育的影响

• 批准号: 9895429
• 负责人: Chad Michael Novince
• 金额: $ 13.59万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9895429
• 关键词: Age; Alveolar Bone Loss; Apoptosis; Autoimmune Diseases; Automobile Driving; Bacteria; Birth; Body Surface; Bone Marrow; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Catabolism; Cell Communication; Cell Count; Cell Differentiation process; Cell Proliferation; Cells; Cellular Immunity; Childhood; Clinical; Deterioration; Development; Developmental Process; Disease; Environment; Estrogens; Exposure to; Genes; Genetic; Genomics; Germ-Free; Growth and Development function; Health; Hematopoiesis; Immune; Immune system; Immunity; In Vitro; Indigenous; Infant; Inflammatory; Inflammatory Bowel Diseases; Interleukin-17; Interleukin-6; Intervention; Investigation; Knowledge; Life; Link; Lymphopoiesis; Marrow; Mediating; Mediator of activation protein; Menopause; Modeling; Mucous Membrane; Mus; Oral cavity; Oral mucous membrane structure; Osteoclasts; Osteogenesis; Osteoporosis; Periodontitis; Periodontium; Peripheral; Phenotype; Population; Process; Publishing; Regulation; Reporting; Research; Risk Factors; Role; Serum; Signal Transduction; Skeletal Development; Skeleton; Stromal Cells; T-Cell Development; T-Lymphocyte; T-Lymphocyte Subsets; TNFSF11 gene; Up-Regulation; Weaning; Work; autoimmune arthritis; bone; bone cell; bone mass; career development; commensal bacteria; commensal microbes; cytokine; experience; germ free condition; gut bacteria; gut colonization; gut microbiome; gut microbiota; host colonization; ileum; immunoregulation; in vivo; interest; microbiome; microbiome research; mineralization; mouse model; normal microbiota; novel; osteoclastogenesis; osteoimmunology; pathogenic bacteria; postdoctoral investigator; postnatal colonization; postnatal development; public health relevance; secondary lymphoid organ; skeletal; stem cells

 DESCRIPTION (provided by applicant): Infants are exposed to commensal (non-pathogenic) bacteria that naturally colonize the gut, oral cavity, and other body surfaces exposed to the external environment. Post-natal colonization of the gut by commensal bacteria regulates the development of the immune system, having lifelong implications for health vs. disease. Of interest, recent genomic studies characterizing the diverse bacteria making up the normal gut flora, have identified distinct commensal bacteria which potently stimulate specific T-lymphocyte immune cell populations during growth & development. While extensive research has focused on the commensal gut flora immuno- regulatory effects in the context of protection against pathogenic bacteria and autoimmune diseases, the commensal flora impact on normal developmental processes is largely unknown. The study of osteoimmunology (*immune cell interactions with bone cells) has shown that specific T- lymphocyte immune cells in the bone marrow regulate bone modeling and remodeling. Despite knowledge that the commensal gut flora directs the development of T-lymphocyte mediated immunity in early post-natal development, there are no known published studies elucidating the commensal gut flora immuno-regulatory effects on pediatric skeletal development. Published findings from the investigator's postdoctoral research work, suggest that commensal flora interactions with the host immune system induce a low level inflammatory state which has catabolic effects in the developing skeleton. The proposed original research investigating the commensal gut flora's immuno-modulatory effects on marrow CD4+/CD8+ T-cell hematopoiesis and bone modeling in the developing GF vs. SPF mouse model is highly relevant in advancing the understanding of normal developmental processes regulating skeletal health. Three specific aims will optimize strong in vitro and in vivo strategies built upon the use of germ-free vs specific- pathogen-free mice to investigate the overall hypothesis that the commensal flora regulates effector CD4+/CD8+ t-cells in the bone environment, having catabolic effects on bone modeling during skeletal development. The first specific aim will investigate the influence of the normal microbiota on osteoblastogenesis; the second specific aim will determine if the osteoclastogenic potential is altered by the commensal flora; the third specific aim will elucidate mechanisms mediating the commensal flora's catabolic effects on skeletal development. This research defining the commensal flora immunomodulatory effects on skeletal development is highly relevant in advancing the understanding of osteoimmunological processes regulating the attainment of peak bone mass, having implications for osteoporosis and periodontitis related skeletal deterioration. Importantly, these studies will provide a strong career development & scientific experience supporting the candidate's transition to scientific independence.



项目成果

Opioid guidelines for common dental surgical procedures: a multidisciplinary panel consensus.

• DOI: 10.1016/j.ijom.2019.09.001
• 发表时间: 2020-03
• 期刊: International journal of oral and maxillofacial surgery
• 影响因子: 2.4
• 作者: Farooqi OA;Bruhn WE;Lecholop MK;Velasquez-Plata D;Maloney JG;Rizwi S;Templeton RB;Goerig A;Hezkial C;Novince CM;Zieman MT;Lotesto AMN;Makary MA
• 通讯作者: Makary MA