Bone is a complex dynamic tissue undergoing a continuous rebuilding-destroying process (remodeling) throughout a lifetime in order to adjust to mechanical demands, to prevent accumulation of fatigue damage, to repair micro-fractures, to ensure the viability of the osteocytes and to participate in calcium homeostasis. The remodeling process is characterized by a rapid resorption and a slower formation phase1. The balance between the amount of bone resorption and bone formation determines whether the process of bone remodelling leads to a net gain or loss of bone mass2-4.
Figure 1. Bone remodeling sequence 5.
Two different cell types play a major role in the process: osteoblasts, the bone-forming cells, and osteoclasts, the bone resorbing cells. Osteoblasts are differentiated cells derived from lining cells, the immediate precursors residing on the bone surface, that regulate the deposition of the bone matrix molecules, including type I collagen and a variety of other non-collagenous proteins. Osteoblasts become osteocytes as soon as a mineralized matrix surrounds them. Instead, osteoclasts, responsible for the mineralized bone matrix resorption, are multinucleated giant cells formed by the fusion of mononuclear progenitors of the monocyte/macrophage lineage1.
Figure 2. Bone cells6.
Mechanical stress is an essential factor to maintain homeostasis and appropriate physiological responses in living bodies. Cells are sensitive to their environment, and can detect both chemical and mechanical signals7,8. During physical activity, mechanical forces are exerted on the bones through ground reaction forces and by the contractile activity of muscles 9,10. These physical forces result in a maintenance or gain of bone mass, but also drive adaptation of bone structure11.
Figure 3. Proposed model for the role of osteocyte-derived Igf1 and Igf1 signaling in mechanotransduction between osteocytes and osteoblasts 12.
Osteocytes are highly mechanosensitive, likely more so than periosteal fibroblasts or osteoblasts, and alter the production of a multitude of signalling molecules when triggered by a mechanical stimulus. Mechanically activated osteocytes produce signalling molecules like bone morphogenetic proteins (BMPs), Wnts, prostaglandin E2 (PGE2), and NO, which can modulate the recruitment, differentiation, and activity of osteoblasts and osteoclasts13-15. In contrast with the increase in bone mass during with vigorous physical exercise16,17, when the skeleton has not to stand against gravity, as it happens during spaceflights, exercise and movements are reduced, leading to a decrease of whole bone mass and density and making bones brittle18.
Because of the paucity of the involved subjects and the limits in the opportunity to study microgravity effects on human bone, several studies related to bone loss in space have been performed taking advantage of rat or mouse models.
- Tavella S, Ruggiu A, Giuliani A, et al. Bone Turnover in Wild Type and Pleiotrophin-Transgenic Mice Housed for Three Months in the International Space Station (ISS). 2012; PLoS ONE 7(3): e33179. doi:10.1371/journal.pone.0033179.
- Vezeridis PS, Semeins CM, Chen Q, et al. Osteocytes subjected to pulsating fluid flow regulate osteoblast proliferation and differentiation. Biochem Biophys Res Commun. 2006; 348: 1082-88.
- You L, Temiyasathit S, Lee P, et al. Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading. Bone. 2008; 42: 172-9.
- Onal M, Xiong J, Chen X, et al. RANKL expression by B lymphocytes contributes to ovariectomy-induced bone loss. J Biol Chem. 2012; 287: 29851-60.
- Available at: http://www.endotext.org/chapter/anatomy-and-ultrastructure-of-bone-histogenesis-growth-and-remodeling/figure6-39/
- Available at: http://www.majordifferences.com/2013/02/difference-between-bone-and-cartilage.html#.VTKxGJPUeMt
- 7. Takano-Yamamoto T. Osteocyte function under compressive mechanical force. Japanese Dental Science Review. 2014; 50: 2, 29–39.
- Hughes-Fulford. Signal transduction and mechanical stress.Sci STKE, 249. 2004; p. RE12.
- Lanyon LE, Hampson WG, Goodship AE, et al. Bone deformation recorded in vivo from strain gauges attached to the human tibial shaft. Acta Orthop Scand. 1975; 46: 256-68.
- Usui T, Maki K, Toki Y, et al. Measurement of mechanical strain on mandibular surface with mastication robot: influence of muscle loading direction and magnitude. Orthod Craniofac Res. 2003; 6(Suppl 1): 163-67; discussion 179-82.
- MECHANICAL LOADING AND HOW IT AFFECTS BONE CELLS:THE ROLE OF THE OSTEOCYTE CYTOSKELETONMAINTAINING OUR SKELETON IN J. Klein-Nulend1,*, R.G. Bacabac2 and A.D. Bakker1. EJu Krolpeiena-nN Culeelnlsd a entd a Ml. a t e r i a l s V o l . 2 4 2 0 1 2 ( p a g e s 2 7 8 – 2 9 1 )
- Available at: : http://ajpendo.physiology.org/content/305/2/E271
- Robling AG, Bellido T, Turner CH. Mechanical stimulation in vivo reduces osteocyte expression of sclerostin. J Musculoskelet Neuronal Interact 6: 354.
- Tan SD, de Vries TJ, Kuijpers-Jagtman AM, et al. Osteocytes subjected to fluid flow inhibit osteoclast formation and bone resorption. Bone. 2007; 41: 745-51.
- Santos A, Bakker AD, Zandieh-Doulabi B, et al . Pulsating fluid flow modulates gene expression of proteins involved in Wnt signaling pathways in osteocytes. J Orthop Res. 2009; 27: 1280-87.
- Globus RK, Bikle DD, Morey-Holton E.The temporal response of bone to unloading. Endocrinology. 1986; 118: 733-42.
- Vandamme K, Holy X, Bensidhoum M. Impaired osteoblastogenesis potential of progenitor cells in skeletal unloading is associated with alterations in angiogenic and energy metabolism profile. Biomed Mater Eng. 2012; 22: 219-26.
- Zhang P, Hamamura K, Yokota H. A brief review of bone adaptation to unloading Genomics Proteomics Bioinformatics. 2008; 6: 4–7.