High Bone Mass Disorders: New Insights from Connecting the Clinic and the Bench

Dylan J M Bergen*, Antonio Maurizi, Melissa M. Formosa, Georgina Mcdonald, Ahmed El-Gazzar, Neelam Hassan, Maria-Luisa Brandi, José A. Riancho, Fernando Rivadeneira, Evangelia Ntzani, Emma L. Duncan, Celia L Gregson, Douglas P. Kiel, M. Carola Zillikens, Luca Sangiorgi, Wolfgang Högler, Ivan Duran, Outi Mäkitie, Wim van Hul, Gretl Hendrickx*

*Corresponding author for this work

Research output: Contribution to journalReview article (Academic Journal)peer-review

4 Citations (Scopus)
50 Downloads (Pure)

Abstract

Monogenic high bone mass (HBM) disorders are characterized by an increased amount of bone in general, or at specific sites in the skeleton. Here, we describe 59 HBM disorders with 50 known disease-causing genes from the literature, and we provide an overview of the signaling pathways and mechanisms involved in the pathogenesis of these disorders. Based on this, we classify the known HBM genes into HBM (sub)groups according to uniform Gene Ontology (GO) terminology. This classification system may aid in hypothesis generation, for both wet lab experimental design and clinical genetic screening strategies. We discuss how functional genomics can shape discovery of novel HBM genes and/or mechanisms in the future, through implementation of omics assessments in existing and future model systems. Finally, we address strategies to improve gene identification in unsolved HBM cases and highlight the importance for cross-laboratory collaborations encompassing multidisciplinary efforts to transfer knowledge generated at the bench to the clinic. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Original languageEnglish
JournalJournal of Bone and Mineral Research
Early online date26 Sept 2022
DOIs
Publication statusE-pub ahead of print - 26 Sept 2022

Bibliographical note

Funding Information:
This publication is initiated upon work from the European Cooperation for Science and Technology (COST) Action GEMSTONE, supported by COST. COST is a funding agency for research and innovation networks. Our Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation ( www.cost.eu ). We therefore thank current and former members of the COST GEMSTONE Working Group 3 ( https://cost-gemstone.eu/working-groups/wg3-monogenic-conditions-human-ko-models/ ) for discussions and support during manuscript preparation. All figures in this manuscript were created with https://biorender.com . DB received funding from Versus Arthritis (Foundation Fellowship, grant # 22044); AM received funding from Fondazione Telethon (GGP20074), the American Society for Bone and Mineral Research (ASBMR Rising Star 2021); MMF is supported by the Malta Council for Science & Technology (GeOM REP‐2020‐011 and MetaBone REP‐2021‐012, for and on behalf of the Foundation for Science and Technology, through the Research Excellence Programme); GMcD is funded by the Wellcome Trust Dynamic Cell doctoral training program (108907/Z/15/Z); NH is funded by the Medical Research Council (Clinical Research Training Fellowship MR/V00199X/1); F.R. is funded by LEGENDARE ERC‐ADG 2020 101021500 grant; I.D. received funding (PID2020‐117255RB‐100); OM received funding from the Sigrid Jusélius Foundation, the Novo Nordisk Foundation and the Academy of Finland; WVH was supported by a Methusalem‐OEC grant—“GENOMED” (Grant Number: FFB190208). The GEMSTONE initiative is funded by the COST action grant #CA18139.

Publisher Copyright:
© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Keywords

  • Bone
  • Osteoblast
  • Rare Diseases/genetics
  • Osteoclasts
  • Omics

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