Bone fracture healing: perspectives according to molecular basis
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PERSPECTIVE
Bone fracture healing: perspectives according to molecular basis Iván Nadir Camal Ruggieri1 · Andrés Mauricio Cícero1 · Joao Paulo Mardegan Issa2 · Sara Feldman1,3 Received: 2 July 2020 / Accepted: 13 October 2020 © The Japanese Society Bone and Mineral Research 2020
Abstract Fractures have a great impact on health all around the world and with fracture healing optimization; this problem could be resolved partially. To make a practical contribution to this issue, the knowledge of bone tissue, cellularity, and metabolism is essential, especially cytoskeletal architecture and its transformations according to external pressures. Special physical and chemical characteristics of the extracellular matrix (ECM) allow the transmission of mechanical stimuli from outside the cell to the plasmatic membrane. The osteocyte cytoskeleton is conformed by a complex network of actin and microtubules combined with crosslinker proteins like vinculin and fimbrin, connecting and transmitting outside stimuli through EMC to cytoplasm. Herein, critical signaling pathways like Cx43-depending ones, MAPK/ERK, Wnt, YAP/TAZ, Rho-ROCK, and others are activated due to mechanical stimuli, resulting in osteocyte cytoskeletal changes and ECM remodeling, altering the tissue and, therefore, the bone. In recent years, the osteocyte has gained more interest and value in relation to bone homeostasis as a great coordinator of other cell populations, thanks to its unique functions. By integrating the latest advances in relation to intracellular signaling pathways, mechanotransmission system of the osteocyte and bone tissue engineering, there are promising experimental strategies, while some are ready for clinical trials. This work aims to show clearly and precisely the integration between cytoskeleton and main molecular pathways in relation to mechanotransmission mechanism in osteocytes, and the use of this theoretical knowledge in therapeutic tools for bone fracture healing. Keywords Bone fracture healing · Mechanical loading · Mechanosensing · Molecular pathway · Osteocyte
Introduction Fractures are a major public health problem worldwide. In addition to morbidity and mortality, fractures result in a high economic cost for health in relation to hospitalization, surgeries, outpatient care and chronic care [1]. The increase in fracture rates can be sustained by several reasons, such as a) change in population lifestyle entails more fracture-promoting accidents, as well as a sedentary lifestyle alters the bone mechanostat; b) in relation to the
* Iván Nadir Camal Ruggieri [email protected] 1
School of Medicine, LABOATEM (Osteoarticular Biology, Tissue Engineering and Emerging Therapies Laboratory), Biological Chemistry Cat, School of Medicine, Rosario National University, Rosario, Argentina
2
São Paulo University, Ribeirão Preto School of Dentistry, Ribeirão Preto, Brazil
3
Research Council of the Rosario National University (CIUNR) and CONICET, Rosario, Argentina
increase in life expectancy, the elderly popula
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