We study osteoimmunology, an interdisciplinary field linking bone biology and immune system, with a focus on the inflammatory regulation of gene expression and signaling in osteoclastogenesis, adipogenesis, skeletal damage and repair involved in diseases, such as osteoporosis and inflammatory arthritis. We utilize genetic approaches (knockout and transgenic mice), a combination of molecular and cellular methods, various next-generation sequencing techniques, multi-omics approaches, and disease models, such as osteoporosis, inflammatory arthritis and high fat diet-induced obesity/type 2 diabetes mouse models. We have worked extensively on signal transduction and crosstalk, genetic and epigenetic regulation of gene expression, cell differentiation and in vivo bone remodeling and metabolism. We have published work at Nature Medicine, Journal of Experimental Medicine, Journal of Clinical Investigation, Journal of Immunology, eLife, and Nature Communications.
Bone destruction is a severe consequence of many skeletal diseases, including the common but refractory diseases, inflammatory arthritis and osteoporosis, and is a major cause of morbidity and disability in rheumatoid arthritis (RA) patients. Our long term goals are to identify and understand the mechanisms that regulate bone remodeling in inflammatory settings, and to develop new therapeutic approaches to suppress pathological bone resorption, recover bone formation and repair skeletal damage based on our discoveries of pathogenic mechanisms and drug targets.
Identification of distinct molecular mechanisms between inflammatory and physiological osteoclastogenesis
Regulation of inflammatory bone remodeling by:
Cross talk between bone and bone marrow adipose, and differential regulation of peripheral and bone marrow adiposity
Discovery of new bone marrow hematopoietic and non-hematopoietic progenitor populations in regulation of skeleton
The Tow Foundation
Arthritis and Tissue Degeneration Program
Inflammatory regulation of bone metabolism
Genetic and epigenetic regulation of gene expression and function
Signal transduction and crosstalk between TNF, TGFbeta, Notch/RBP-J, IFN, ITAM and RANKL signaling pathways
Discovery of previously unrecognized bone marrow progenitors
Associate Professor, Department of Medicine, Weill Medical College of Cornell University
Associate Professor, Graduate Program in Cell & Developmental Biology, Weill Medical College of Cornell University
Associate Scientist, Arthritis and Tissue Degeneration Program, Hospital for Special Surgery
Department of Medicine, Weill Medical College of Cornell University
Graduate Program in Cell & Developmental Biology, Weill Medical College of Cornell University
PhD, Showa University, Japan
DMD, Peking University, China
BM, Peking University, China
NIH/NIAMS Pathway to Independence Award (2012)
Osteoimmunology Young Investigator Award (Greece 2012)
Harold M. Frost Young Investigator Award (2011)
John Haddad Young Investigator Award (AIMM 2010)
ASBMR Young Investigator Award (2007)
English, Chinese, Japanese
Xia Y, Inoue K, Du Y, Baker S, E. Reddy EP, Greenblatt M, Zhao B. TGFβ reprograms TNF stimulation of macrophages towards a non-canonical pathway driving inflammatory osteoclastogenesis, Nature Communications 13, 3920 (2022). https://doi.org/10.1038/s41467-022-31475-1 *Highlighted by 2021 ASBMR annual meeting; *ASBMR Webster Jee Award.
Deng Z, Ng C, Inoue K, Chen Z, Xia Y, Hu X, Greenblatt M, Pernis A and Zhao B. Def6 regulates endogenous type I interferon responses in osteoblasts and suppresses osteogenesis. eLife, 2020; 9: e59659. PMID: 33373293 PMC7771961
Inoue K, Hu X, Zhao B. Regulatory network mediated by RBP-J/NFATc1-miR182 controls inflammatory bone resorption. FASEB J. 2020;34(2):2392-2407. doi: 10.1096/fj.201902227R.
Xu C, Vitone G, Inoue K, Ng C, Zhao B. Identification of a novel role for Foxo3 isoform2 in osteoclastic inhibition. Journal of Immunology, 2019 Oct 15;203(8):2141-2149. *Featured cover article in the Journal of Immunology 2019
Nakano S, Inoue K, Xu C, Deng Z, Syrovatkina V, Vitone G, Zhao L, Huang XY, Zhao B. G-protein Gα13 functions as a cytoskeletal and mitochondrial regulator to restrain osteoclast function. Scientific Report, 2019 Mar 12;9(1):4236.
Inoue K, Deng Z, Chen Y, Giannopoulou E, Xu R, Gong S, Greenblatt MB, Mangala LS, Lopez-Berestein G, Kirsch DG, Sood AK, Zhao L, Zhao B. Bone protection by inhibition of microRNA-182. Nature Communications, 2018 Oct 5;9(1):4108.
*Featured in Nature Communications Editors' Highlights 2018
*Highlighted by Editorial Commentary: Fassan M, Vicentini C. Role of microRNA-182 in skeletal diseases: new therapeutic approaches to prevent bone loss. Non-coding RNA Investig 2019;3:9.
Binder N, Miller C, Yoshida M, Inoue K, Nakano S, Hu X, Ivashkiv L, Schett G, Pernis A, Goldring SR, Ross FP, Zhao B. Def6 restrains osteoclastogenesis and inflammatory bone resorption, Journal of Immunology 2017 ;198(9):3436-3447.
Miller C, Smith S, Elguindy M, Zhang T, Xiang J, Hu X, Ivashkiv LB, Zhao B. RBP-J-regulated miR-182 promotes TNF-a-induced osteoclastogenesis. Journal of Immunology 2016, 196(12):4977-86. *Featured in the Journal of Immunology 2016
Li S, Miller C, Giannopoulou E, Hu X, Ivashkiv L , Zhao B. RBP-J imposes a requirement for ITAM-mediated costimulation of osteoclastogenesis. Journal Clinical Investigation. 2014 Nov 3;124(11):5057-73.
*Featured on the NIAMS home page as the June 2015 Spotlight on Research:
Zhao B, Takami M, Yamada A, Wang X, Koga T, Hu X, Tamura T, Ozato K, Choi Y, Ivashkiv LB, Takayanagi H, Kamijo R. Interferon regulatory factor 8 regulates bone metabolism by suppressing osteoclastogenesis. Nature Medicine 2009; 15: 1066-1071.
*Highlighted in the article "Bone diseases: Interferon regulatory factor-8 suppresses
osteoclastogenesis" in Nature Reviews Rheumatology 6, 73-74 (February 2010)
*Recommended by Faculty of 1000 Medicine on Oct 9, 2009.
*Highlighted in the Bulletin Board of Int. J. Clin. Rheumatol. 2009, 4, 5.
For more publications, please see the PubMed listing
Invited Speaker, "A non-canonical, RANKL-independent pathway drives inflammatory osteoclastogenesis", Advances in Mineral Metabolisms (AIMM), Snowmass, Colorado, April 2022
Invited Seminar, "When the Bone Meets Inflammation", Icahn School of Medicine at Mount Sinai, New York, June 2022
Invited Seminar, "Non-canonical Mechanisms Drive Inflammatory Osteoclastogenesis", University of Pennsylvania School of Medicine, April 2022
Invited Speaker, "Molecular Regulation of Type-1-Interferon to Regulate Osteoblasts and Osteoclasts", American College of Rheumatology (ACR) Convergence, San Francisco, CA, Nov 2021
Invited Seminar, "Endogenous type-I IFN signaling in osteoblasts and osteogenesis", University of Missouri-Kansas City, June 2021
Spotlight Speaker, "Type-1-Interferon in osteoblasts and osteogenesis", American Society for Bone and Mineral Research Member Spotlight Series, May 2021
Invited featured Seminar, "FoxO3 is a novel type-I IFN activator", Immunity and Immunochemistry conference, Oct 2020
Invited Seminar, "FoxO3 Isoform2: A Novel Player in IFN-I Activation and Osteoclastic Inhibition", North Carolina University, November 2019
Invited Seminar, "Mechanisms of inflammatory osteoclastogenesis and bone resorption", Northwestern University, June 2018
Invited speaker, "MicroRNAs control osteoclastogenesis and bone remodeling", Seventh International Conference on Osteoimmunology: Interactions of the Immune and Skeletal Systems, Greece, June 2018
One of the goals of HSS is to advance the science of orthopedic surgery, rheumatology, and related disciplines for the benefit of patients. Research staff at HSS may collaborate with outside companies for education, research and medical advances. HSS supports this collaboration in order to foster medical breakthroughs; however, HSS also believes that these collaborations must be disclosed.
As part of the disclosure process, this website lists Research staff collaborations with outside companies if the Research staff member received any payment during the prior year or expects to receive any payment in the next year. The disclosures are based on information provided by the Research staff and other sources and are updated regularly. Current ownership interests and leadership positions are also listed. Further information may be available on individual company websites.
As of April 27, 2020, Dr. Zhao reported no relationships with healthcare industry.
By disclosing the collaborations of HSS Research staff with industry on this website, HSS and its Research staff make this information available to patients and the public, thus creating a transparent environment for those who are interested in this information. Further, the HSS Conflicts of Interest Policy does not permit payment of royalties on products developed by him/her that are used on patients at HSS.