The coupling of bone remodeling to energy metabolism
Live Webinar: 26 November 2020, 4pm CET
Organised by ECTS and ECTS Academy.
Date & Time: 26 November 2020, 4pm CET
Featuring Megan Weivoda, and moderated by Martina Rauner
Costs: Live webinar is free for ECTS members and non-members, but a registration is required. Recordings are accessible to ECTS members only.
- 5 min welcome & introductions
- 35 min presentation
- 20 min Q&A
- Anti-RANKL mediated disruption of bone resorption leads to a coupling-related decrease in bone formation at the gene expression level
- Bone cells exhibit changes in energy metabolism that correlate with differentiation and/or functional status
- Bone resorption and formation correlate with metabolic markers, suggesting a potential coupling of bone remodeling to energy metabolism.
Featuring Megan Weivoda
Megan Weivoda is an Assistant Professor in the Department of Periodontics and Oral Medicine at the University of Michigan School of Dentistry. She received her PhD in Pharmacology at the University of Iowa, completed a visiting fellowship at the University of Oxford and postdoctoral research at the Mayo Clinic in Rochester, Minnesota. Dr Weivoda previously served as Assistant Professor in the Division of Endocrinology at the Mayo Clinic. Her research programme focuses on the role of osteoclasts in the bone remodelling cycle. Specifically, she is investigating the mechanisms by which osteoclast-mediated bone resorption activates subsequent cycles of bone formation and how this “coupling” is disrupted during ageing in order to identify novel mechanisms to stimulate bone formation. In addition, her lab is investigating the connections of ageing and senescence to cancer and inflammatory diseases. Dr Weivoda is a member of the American Society for Bone and Mineral Research (ASBMR) and the International Association for Dental Research (IADR), and currently serves as Co-Chair of the ASBMR Early Stage Investigator Subcommittee.
Moderated by Martina Rauner
Martina Rauner studied biotechnology in Vienna, Austria. After completing her doctorate in Molecular Endocrinology in 2008, she received the ECTS/AMGEN bone research fellowship and joined the group of Professor Lorenz Hofbauer in Dresden, Germany to study mechanisms of glucocorticoid-induced osteoporosis. In 2011, Martina became Group leader for Osteoimmunology and expanded her research area to chronic inflammatory diseases and Wnt signaling. She was promoted to the Scientific Director of the Bone lab in 2015 and became Professor for Molecular Bone Biology in 2018. Her group is particularly interested in the interactions of bone with hematopoiesis and hormones, and studies the role of Wnt and BMP signaling.
Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts; this coupling of resorption to formation is hypothesized to depend on osteoclast-derived coupling factors that stimulate osteoblast differentiation and bone formation. We utilized denosumab (DMAb) to pharmacologically ablate osteoclasts in post-menopausal women and test the “coupling-factor hypothesis” in humans. RNA-sequencing of bone biopsies from placebo or DMAb-treated participants revealed osteoclast-secreted factors suppressed by DMAb. Based on these analyses, LIF, CREG2, CST3, CCBE1, and DPP4 are likely osteoclast-derived coupling factors in humans. Given the role of Dipeptidyl Peptidase-4 (DPP4) in glucose homeostasis, we further evaluated serum metabolic markers and determined that DMAb-treated participants have a significant reduction in circulating DPP4 and increase in Glucagon-like peptide (GLP)-1 levels as compared to the placebo-treated group. In addition, type 2 diabetic patients treated with DMAb showed significant reductions in HbA1c as compared to patients treated with either bisphosphonates or calcium and vitamin D. Thus, our results identify several potential osteoclast-derived coupling factors in humans and uncover osteoclast-derived DPP4 as a potential link to coordinate bone remodeling and energy metabolism.