Bone's response to mechanical loading in aging and osteoporosis:​ molecular mechanisms

Carina, Valeria; Della Bella, Elena; Costa, Viviana; Bellavia, Daniele; Veronesi, Francesca; Cepollaro, Simona; Fini, Milena; Giavaresi, Gianluca

Affiliations

¹IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche - SS Piattaforma Scienze Omiche per Ortopedia Personalizzata, Bologna, Italy

²AO Research Institute Davos, Davos, Switzerland

Abstract and keywords

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.

Keywords: Aging; Bone; Mechanotransduction; Osteoporosis; Signaling

Links

DOI: 10.1007/s00223-020-00724-0

PubMed: 32710266

WoS: 000552176300001

History

Received: 2020-04-24

Accepted: 2020-07-08

Online: 2020-07-24

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2022	Anani T, Castillo AB. Mechanically-regulated bone repair. Bone. January 2022;154:116223.
2022	Zhang J, Tong Y, Liu Y, Lin M, Xiao Y, Liu C. Mechanical loading attenuated negative effects of nucleotide analogue reverse-transcriptase inhibitor TDF on bone repair via Wnt/β-catenin pathway. Bone. August 2022;161:116449.
2022	Ma J, Wang A, Zhang H, Liu B, Geng Y, Xu Y, Zuo G, Jia P. Iron overload induced osteocytes apoptosis and led to bone loss in Hepcidin^−/− mice through increasing sclerostin and RANKL/OPG. Bone. November 2022;164:116511.