Bone's Response to Mechanical Loading in Aging and Osteoporosis: Molecular Mechanisms
- PDF / 1,252,218 Bytes
- 18 Pages / 595.276 x 790.866 pts Page_size
- 36 Downloads / 158 Views
REVIEW ARTICLE
Bone’s Response to Mechanical Loading in Aging and Osteoporosis: Molecular Mechanisms Valeria Carina1 · Elena Della Bella2 · Viviana Costa1 · Daniele Bellavia1 · Francesca Veronesi1 · Simona Cepollaro1 · Milena Fini1 · Gianluca Giavaresi1 Received: 24 April 2020 / Accepted: 8 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Aging · Bone · Mechanotransduction · Osteoporosis · Signaling
Introduction During human growth, bone tissue continues to adapt to changes in mechanical loads [1–4]. Its growth is mediated by the continuous activity of osteoblasts (OB) (bone deposition) and osteoclasts (OCs) (bone resorption), and the control of osteocytes that act as “sensor” of stimuli and convert mechanical stress into biological signals (bone homeostasis) [1]. The presence or absence (disuse/unloading) of mechanical forces on bone, result in different cellular adaptations that convert the external stimuli into internal cellular responses— the cellular mechanotransduction process. The conversion of external forces into biochemical and biological signaling involves four different elements: force transmission to cells * Valeria Carina [email protected] 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
AO Research Institute Davos, Davos, Switzerland
2
(i.e., hydrostatic pressure, fluid shear stress, and direct deformation), mechanosensing, signal transduction and signal transmission [2, 5–8]. In particular, the analysis of cellular mechanotransduction was concentrated on mechanosensitive molecules identification and c
Data Loading...
