OsteoImmunology

How Bone and the Immune System communicate

A wide variety of chronic inflammatory diseases cause bone loss. To understand this phenomenon, the Bone Lab focuses on two common diseases: rheumatoid arthritis, a chronic inflammation of the joints, and periodontitis, an inflammation of the tooth-supporting structures. In rheumatoid arthritis, which affects 1-2% of the population, joints and bones are damaged and mobility is lost. Periodontitis affects almost 50% of the aging population and leads to tooth loss. Both diseases considerably impair life quality.

Our aim is to better understand the interactions between the immune and skeletal system and identify novel molecular targets that may be used to treat bone loss caused by inflammation. An important topic of this research area is glucocorticoid-induced osteoporosis (GIO). Glucocorticoids are amongst the most commonly described drugs to treat inflammatory diseases. Even though they are very potent and offer patients quick relief of pain and swelling, their long-term use is associated with poor bone quality. Our ambition is to understand what drives bone loss in inflammation and glucocorticoid treatment in order to minimize it in the future.

Principal Investigators

Martina Rauner, PhD

«Was my first love… the collaborations within the Immunobone consortium really pushed my career»

Ulrike Baschant, PhD

«I would call it my scientific home.»

Team

: Tina Dybek, B.Sc.

: Ina Gloe, B.Sc.

: María Ledesma-Colunga, PhD

: Christiane Schirm, B.Sc.

: Zsófia Szábo, B.Sc.

Collaborations

Jan Tuckermann, Universität Ulm
Georg Schett, Universität Erlangen-Nürnberg
Maxime Breban, Institut Cochin, Paris, France
Triantaphyllos Chavakis, Technische Universität Dresden
Anke Hannemann, Universität Greifswald
Nicole Horwood, Oxford University, UK

Publications

Gado M, Heinrich A, Wiedersich D, Sameith K, Dahl A, Alexaki VI, Swarbrick MM, Baschant U, Grafe I, Perakakis N, Bornstein SR, Rauner M, Hofbauer LC, Henneicke H. Activation of beta-adrenergic receptor signaling prevents glucocorticoid-induced obesity and adipose tissue dysfunction in male mice. Am J Physiol Endocrinol Metab. 2023 Apr 26.

Reckelkamm SL, Hannemann A, Kocher T, Nauck M, Völzke H, Ehmke B, Rauner M, Alayash Z, Baumeister SE, Nolde M, Holtfreter B. Association between bone turnover markers and periodontitis: A population-based cross-sectional study. J Clin Periodontol. 2022;49:633-641.

Baschant U, Hauser B, Winter EM. Editorial: Glucocorticoid and bone: Friend or foe. Front Endocrinol (Lausanne). 2022;13:995124.

Gado M, Baschant U, Hofbauer LC, Henneicke H. Bad to the Bone: The Effects of Therapeutic Glucocorticoids on Osteoblasts and Osteocytes. Front Endocrinol (Lausanne). 2022;13:835720.

Hayes KN, Baschant U, Hauser B, Burden AM, Winter EM. Corrigendum: When to Start and Stop Bone-Protecting Medication for Preventing Glucocorticoid-Induced Osteoporosis. Front Endocrinol (Lausanne). 2022;13:877512. Erratum for: Front Endocrinol (Lausanne). 2021;12:782118.

Hayes KN, Baschant U, Hauser B, Burden AM, Winter EM. When to Start and Stop Bone-Protecting Medication for Preventing Glucocorticoid-Induced Osteoporosis. Front Endocrinol (Lausanne). 2021;12:782118. Erratum in: Front Endocrinol (Lausanne). 2022;13:877512.

Tsourdi E, Hofbauer LC, Rauner M. The Impact of COVID-19 in Bone Metabolism: Basic and Clinical Aspects. Horm Metab Res. 2022;54:540-548.

McDonald MM, Kim AS, Mulholland BS, Rauner M. New Insights Into Osteoclast Biology. JBMR Plus. 2021;5:e10539.

Kim S, Henneicke H, Cavanagh LL, Macfarlane E, Thai LJ, Foong D, Gasparini SJ, Fong-Yee C, Swarbrick MM, Seibel MJ, Zhou H. Osteoblastic glucocorticoid signaling exacerbates high-fat-diet- induced bone loss and obesity. Bone Res. 2021 1;9:40.

Schündeln MM, Höppner J, Meyer FL, Schmuck W, Kauther MD, Hilken G, Levkau B, Rauner M, Grasemann C. Prednisone prevents particle induced bone loss in the calvaria mouse model. Heliyon. 2021 18;7:e07828.

Furesi G, Fert I, Beaufrère M, Araujo LM, Glatigny S, Baschant U, von Bonin M, Hofbauer LC, Horwood NJ, Breban M, Rauner M. Rodent Models of Spondyloarthritis Have Decreased White and Bone Marrow Adipose Tissue Depots. Front Immunol. 2021 2;12:665208.

Lehmann J, Thiele S, Baschant U, Rachner TD, Niehrs C, Hofbauer LC, Rauner M. Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss. iScience. 2021 23;24:102224.

Yu EW, Tsourdi E, Clarke BL, Bauer DC, Drake MT. Reply to corticosteroid-induced osteonecrosis in COVID-19: a call for caution. J Bone Miner Res. 2020;35(10):2084-2085.

Alexaki VI, Henneicke H. The Role of Glucocorticoids in the Management of Covid-19. Horm Metab Res. 2021 Jan;53(1):9-15.

Henneicke H, Kim S, Swarbrick MM, Li J, Gasparini SJ, Thai J, Foong D, Cavanagh LL, Fong-Yee C, Karsten E, Lin RCY, Cooper MS, Zhou H, Seibel MJ. Skeletal glucocorticoid signalling determines leptin resistance and obesity in aging mice. Mol Metab. 2020;42:101098

Thiele S, Hannemann A, Winzer M, Baschant U, Weidner H, Nauck M, Thakker RV, Bornhäuser M, Hofbauer LCand Rauner M. Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humans. Endocr Connect. 2019;8(7):923-934.

Colditz J, Thiele S, Baschant U, Garbe AI, Niehrs C, Hofbauer LC, Rauner M. Osteogenic Dkk1 mediates glucocorticoid-induced but not arthritis-induced bone loss. J Bone Miner Res. 2019.

Thiele S, Rauner M, Goes P Recent advances in periodontitis, a prototypic osteo-immunological disease. JLPM. 2018

Koenen M, Culemann S, Vettorazzi S, Caratti G, Frappart L, Baum W, Krönke G, Baschant U, Tuckermann JP. Glucocorticoid receptor in stromal cells is essential for glucocorticoid-mediated suppression of inflammation in arthritis. Ann Rheum Dis. 2018; 77:1610-18.

Hildebrandt S, Baschant U, Thiele S, Tuckermann J, Hofbauer LC, Rauner M. Glucocorticoids suppress Wnt16 expression in osteoblasts in vitro and in vivo. Sci Rep. 2018;8:8711.

Geurtzen K, Vernet A, Freidin A, Rauner M, Hofbauer LC, Schneider JE, Brand M, Knopf F. Immune suppressive and bone inhibitory effects of prednisolone in growing and regenerating zebrafish tissues. J Bone Miner Res. 2017;32:2476-2488.

Schulz MC, Kowald J, Estenfelder S, Jung R, Kuhlisch E, Eckelt U, Mai R, Hofbauer LC, Stroszczynski C, Stadlinger B. Site-specific variations in bone mineral density under systemic conditions inducing osteoporosis in minipigs. Front Physiol. 2017;8:426.

Liu P, Baumgart M, Groth M, Wittmann J, Jäck HM, Platzer M, Tuckermann JP, Baschant U. Dicer ablation in osteoblasts by Runx2 driven cre-loxP recombination affects bone integrity, but not glucocorticoid-induced suppression of bone formation. Sci Rep. 2016;6:32112.

Rauner M, Thiele S, Sinningen K, Winzer M, Salbach-Hirsch J, Gloe I, Peschke K, Haegeman G, Tuckermann JP, Hofbauer LC. Effects of the selective glucocorticoid receptor modulator A compound on bone metabolism and inflammation in male mice with collagen-induced arthritis. Endocrinology. 2013;154:3719-28.

Research Question

Which immune mechanisms account for the damage of inflammation on bone? Why do glucocorticoids that are used to suppress inflammation harm bone strength? Our combined expertise in bone biology and immunology allows addressing these questions.

Approach

We use several preclinical models that closely recapitulate human disease, including transgenic and knock out mice with cell-specific and global genetic deletion. These models are challenged to develop immune phenotypes and/or exposed to glucocorticoids before their phenotype is comprehensively assessed.

Projects

Role of Dickkopf-1 (Dkk-1) in the inflammatory process of postmenopausal osteoporosis
Role of Wnt signaling in arthritis and glucocorticoid-induced osteoporosis
Role of Dkk1 in periodontitis
Impact of inflammation on bone marrow fat
The effects of glucocorticoid excess on the osteohematopoietic niche

Funding

This research field is supported by several project grants from Deutsche Forschungsgemeinschaft.