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Bone's Response to Mechanical Loading in Aging and Osteoporosis: Molecular Mechanisms

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Abstract

Mechanotransduction is pivotal in the maintenance of homeostasis in different tissues and involves multiple cell signaling pathways. In bone, mechanical stimuli regulate the balance between bone formation and resorption; osteocytes play a central role in this regulation. Dysfunctions in mechanotransduction signaling or in osteocytes response lead to an imbalance in bone homeostasis. This alteration is very relevant in some conditions such as osteoporosis and aging. Both are characterized by increased bone weakness due to different causes, for example, the increase of osteocyte apoptosis that cause an alteration of fluid space, or the alteration of molecular pathways. There are intertwined yet very different mechanisms involved among the cell-intrinsic effects of aging on bone, the cell-intrinsic and tissue-level effects of estrogen/androgen withdrawal on bone, and the effects of reduced mechanical loading on bone, which are all involved to some degree in how aged bone fails to respond properly to stress/strain compared to younger bone. This review aims at clarifying how the cellular and molecular pathways regulated and induced in bone by mechanical stimulation are altered with aging and in osteoporosis, to highlight new possible targets for antiresorptive or anabolic bone therapeutic approaches.

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Acknowledgements

Valeria Carina, Viviana Costa and Daniele Bellavia contributed to the manuscript by working at the Technology Platform of Tissue Engineering, Theranostic and Oncology (Lab. Manager Dr. Gianluca Giavaresi), a laboratory started up by the Rizzoli Orthopedic Institute in Palermo (Italy) with the grants also of National Operative Program projects (PON). AO Foundation.

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No benefits in any form were received or will be received from a commercial party.

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  1. IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche - SS Piattaforma Scienze Omiche per Ortopedia Personalizzata, Via Di Barbiano, 1/10, 40136, Bologna, Italy

    Valeria Carina, Viviana Costa, Daniele Bellavia, Francesca Veronesi, Simona Cepollaro, Milena Fini & Gianluca Giavaresi

  2. AO Research Institute Davos, Davos, Switzerland

    Elena Della Bella

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  1. Valeria Carina
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Contributions

All authors contributed to the study conception and design. VC, EDB, MF, and GG had the idea for the article, VC, EDB, VC, DB, and SC performed the literature search and data analysis, VC, EDB, VC, and DB drafted the work. Finally, FV, MF and GG critically revised the work. All authors red and approved the final manuscript.

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Correspondence to Valeria Carina.

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Valeria Carina, Elena Della Bella, Viviana Costa, Daniele Bellavia, Francesca Veronesi, Simona Cepollaro, Milena Fini, Gianluca Giavaresi, declare that they have no conflict of interest.

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Carina, V., Della Bella, E., Costa, V. et al. Bone's Response to Mechanical Loading in Aging and Osteoporosis: Molecular Mechanisms. Calcif Tissue Int 107, 301–318 (2020). https://doi.org/10.1007/s00223-020-00724-0

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