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

doi:10.1002/jbmr.4715

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 journal › Review article (Academic Journal) › peer-review

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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 language	English
Journal	Journal of Bone and Mineral Research
Early online date	26 Sept 2022
DOIs	https://doi.org/10.1002/jbmr.4715
Publication status	E-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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Bergen, D. J. M., Maurizi, A., Formosa, M. M., Mcdonald, G., El-Gazzar, A., Hassan, N., Brandi, M.-L., Riancho, J. A., Rivadeneira, F., Ntzani, E., Duncan, E. L., Gregson, C. L., Kiel, D. P., Zillikens, M. C., Sangiorgi, L., Högler, W., Duran, I., Mäkitie, O., van Hul, W., & Hendrickx, G. (2022). High Bone Mass Disorders: New Insights from Connecting the Clinic and the Bench. Journal of Bone and Mineral Research. Advance online publication. https://doi.org/10.1002/jbmr.4715

@article{b32c7b1e95a44e38a2ba2c3720ebb37e,

title = "High Bone Mass Disorders: New Insights from Connecting the Clinic and the Bench",

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. {\textcopyright} 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",

author = "Bergen, {Dylan J M} and Antonio Maurizi and Formosa, {Melissa M.} and Georgina Mcdonald and Ahmed El-Gazzar and Neelam Hassan and Maria-Luisa Brandi and Riancho, {Jos{\'e} A.} and Fernando Rivadeneira and Evangelia Ntzani and Duncan, {Emma L.} and Gregson, {Celia L} and Kiel, {Douglas P.} and Zillikens, {M. Carola} and Luca Sangiorgi and Wolfgang H{\"o}gler and Ivan Duran and Outi M{\"a}kitie and {van Hul}, Wim and Gretl Hendrickx",

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 Jus{\'e}lius 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: {\textcopyright} 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).",

year = "2022",

month = sep,

day = "26",

doi = "10.1002/jbmr.4715",

language = "English",

journal = "Journal of Bone and Mineral Research",

issn = "0884-0431",

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}

Bergen, DJM, Maurizi, A, Formosa, MM, Mcdonald, G, El-Gazzar, A, Hassan, N, Brandi, M-L, Riancho, JA, Rivadeneira, F, Ntzani, E, Duncan, EL, Gregson, CL, Kiel, DP, Zillikens, MC, Sangiorgi, L, Högler, W, Duran, I, Mäkitie, O, van Hul, W & Hendrickx, G 2022, 'High Bone Mass Disorders: New Insights from Connecting the Clinic and the Bench', Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.4715

TY - JOUR

T1 - High Bone Mass Disorders

T2 - New Insights from Connecting the Clinic and the Bench

AU - Bergen, Dylan J M

AU - Maurizi, Antonio

AU - Formosa, Melissa M.

AU - Mcdonald, Georgina

AU - El-Gazzar, Ahmed

AU - Hassan, Neelam

AU - Brandi, Maria-Luisa

AU - Riancho, José A.

AU - Rivadeneira, Fernando

AU - Ntzani, Evangelia

AU - Duncan, Emma L.

AU - Gregson, Celia L

AU - Kiel, Douglas P.

AU - Zillikens, M. Carola

AU - Sangiorgi, Luca

AU - Högler, Wolfgang

AU - Duran, Ivan

AU - Mäkitie, Outi

AU - van Hul, Wim

AU - Hendrickx, Gretl

N1 - 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).

PY - 2022/9/26

Y1 - 2022/9/26

N2 - 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).

AB - 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).

KW - Bone

KW - Osteoblast

KW - Rare Diseases/genetics

KW - Osteoclasts

KW - Omics

UR - https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4715

U2 - 10.1002/jbmr.4715

DO - 10.1002/jbmr.4715

M3 - Review article (Academic Journal)

C2 - 36161343

SN - 0884-0431

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

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Other files and links

Fingerprint

Regenerating zebrafish scales express a subset of evolutionary conserved genes involved in human skeletal disease

A Roadmap to Gene Discoveries and Novel Therapies in Monogenic Low and High Bone Mass Disorders

Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques

Functional validation of novel osteo-anabolic factors in the zebrafish

Determining new osteo-anabolic targets using zebrafish models of human genomic study discoveries.

Cite this

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

Abstract

Bibliographical note

Keywords

Access to Document

Handle.net

Other files and links

Fingerprint

Research output

Regenerating zebrafish scales express a subset of evolutionary conserved genes involved in human skeletal disease

A Roadmap to Gene Discoveries and Novel Therapies in Monogenic Low and High Bone Mass Disorders

Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques

Projects

Functional validation of novel osteo-anabolic factors in the zebrafish

Activities

Determining new osteo-anabolic targets using zebrafish models of human genomic study discoveries.

Cite this