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Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies

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Abstract

Several metabolic, genetic and oncogenic bone diseases are characterized by defective or excessive bone formation. These abnormalities are caused by dysfunctions in the commitment, differentiation or survival of cells of the osteoblast lineage. During the recent years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the osteoblast dysfunctions in osteoporosis, skeletal dysplasias and primary bone tumors. This led to suggest novel therapeutic approaches to correct these abnormalities such as the modulation of WNT signaling, the pharmacological modulation of proteasome-mediated protein degradation, the induction of osteoprogenitor cell differentiation, the repression of cancer cell proliferation and the manipulation of epigenetic mechanisms. This article reviews our current understanding of the major cellular and molecular mechanisms inducing osteoblastic cell abnormalities in age-related bone loss, genetic skeletal dysplasias and primary bone tumors, and discusses emerging therapeutic strategies to counteract the osteoblast abnormalities in these disorders of bone formation.

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Acknowledgments

The author thanks all members of his group Osteoblast Biology and Pathology who contributed to the work reviewed in this paper, and apologizes to the investigators whose work could not be cited due to space limitations. The author’s work was supported by Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Médicale (Inserm), University Paris Diderot, European Commission programs (FP76, FP7), European Calcified Tissue Society (ECTS), Agence Nationale de la Recherche (ANR), Centre National d’Etudes Spatiales (CNES), DIM Stem Pôle Ile de France, Fondation de l’Avenir pour la Recherche Appliquée, Association Recherche contre le Cancer (ARC), Fondation pour la Recherche Médicale (FRM), Société Française de Rhumatologie (SFR), Association Prévention et Traitement des Décalcifications (PTD) and Association Rhumatisme et Travail (Paris, France). Figures were produced using Servier Medical Art.

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  1. INSERM UMR-1132, Hôpital Lariboisière, 2 rue Ambroise Paré, 75475, Paris Cedex 10, France

    Pierre J. Marie

  2. Université Paris Diderot, Sorbonne Paris Cité, Paris, France

    Pierre J. Marie

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Marie, P.J. Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies. Cell. Mol. Life Sci. 72, 1347–1361 (2015). https://doi.org/10.1007/s00018-014-1801-2

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