Fig 4 - uploaded by Carla Palumbo
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Enlargement of the squared area in Fig. 3. The insert (top left) clarifies the type of the tangential-longitudinal section of the osteocyte canaliculus, along the intracanalicular–pericytoplasmic space; in gray is shown the osteocyte process (not cut by the tangential-longitudinal section). Transmission electron microscopy (TEM) micrograph shows the fibrillar/proteoglycan atmosphere surrounding an osteocyte cytoplasmic process (not visible in the photograph) inside an osteocyte canaliculus at its origin from the osteocyte lacuna (white arrows). Note the thin fibrillar components (along with and in between proteoglycans are known to be located) as a connection between the osteocyte canaliculus wall (asterisks) and the cytoplasmic process (not visible). Note also proteoglycan tethering elements (black arrows) bridging osteocyte cell process (not visible) to bony canalicular wall. The discrete protrusions from the canalicular wall (matrix hillock protrusions – white head arrows) are visible protruding towards the pericytoplasmic space. N, osteocyte nucleus.
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Hitherto, the role of the osteocyte as transducer of mechanical stimuli into biological signals is far from settled. In this study, we used an appropriate model represented by the cortex of Xenopus laevis long bone diaphysis lacking (unlike the mammalian one) of vascular structures and containing only osteocytes inside the bone matrix. These struct...
Citations
... Thus, increasing attention is now turning towards protein changes in osteoporosis. Currently, proteomic analyses to identify protein signature of osteoporosis have been performed on human serum and bone-related cell lines (18)(19)(20)(21)(22), but the proteomic analysis of osteoporosis with iron accumulation has not been conducted in human bone. ...
Iron accumulation is an independent risk factor for postmenopausal osteoporosis, but mechanistic studies of this phenomenon are still focusing on molecular and genetic researches in model animal. Osteoporosis with iron accumulation is a distinct endocrine disease with complicated pathogenesis regulated by several proteins. However, the comprehensive proteome-wide analysis of human bone is lacking. Using multiplex quantitative tandem mass tag-based proteomics, we detected 2900 and quantified 1150 proteins from bone of 10 postmenopausal patients undergoing hip replacement. Comparing with non-osteoporosis patients, a total of 75 differentially expressed proteins were identified, comprising 53 downregulated proteins and 22 upregulated proteins. These proteins primarily affect oxidoreductase activity, GTPase activity, GTP binding, and neural nucleus development, were mainly enriched in neural, angiogenesis and energy-related pathways, and formed complex regulatory networks with strong interconnections. We ultimately identified 4 core proteins (GSTP1, LAMP2, COPB1, RAB5B) that were significantly differentially expressed in the bone of osteoporosis patients with iron accumulation, and validated the changed protein level in the serum of the medical examination population. Our systemic analysis uncovers molecular insights for revealing underlying mechanism and clinical therapeutics in osteoporosis with iron accumulation.
... As regards the transmission of mechanical signals, both recent and less recent literature indicates the osteocyte as the main strain-sensitive bone cell [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58]. We have shown [42,43] that shear stress-activated osteocytes are capable of steadily increasing and maintaining the basal current produced by the ionic fluxes (streaming potentials), which occur inside the lacuno-canalicular microcavities in response to pulsing mechanical loading ( Figure 8). ...
... Recently [58], as far as the bone adaptation-related cell-signaling is concerned, both Erk1/2 and Akt were showed to be hyperphosphorylated in frog long bones of stressed samples (forced swimming) suggesting that among the putative osteocyte signal transduction mechanisms, Akt signaling is boosted by increased mechanical stresses. Moreover, the authors confirmed again that the increase of osteocyte gap junction number is dependent on mechanical loading ( Figure 10). ...
Osteocytes are the most abundant bone cells, entrapped inside the mineralized bone matrix. They derive from osteoblasts through a complex series of morpho-functional modifications; such modifications not only concern the cell shape (from prismatic to dendritic) and location (along the vascular bone surfaces or enclosed inside the lacuno-canalicular cavities, respectively) but also their role in bone processes (secretion/mineralization of preosseous matrix and/or regulation of bone remodeling). Osteocytes are connected with each other by means of different types of junctions, among which the gap junctions enable osteocytes inside the matrix to act in a neuronal-like manner, as a functional syncytium together with the cells placed on the vascular bone surfaces (osteoblasts or bone lining cells), the stromal cells and the endothelial cells, i.e., the bone basic cellular system (BBCS). Within the BBCS, osteocytes can communicate in two ways: by means of volume transmission and wiring transmission, depending on the type of signals (metabolic or mechanical, respectively) received and/or to be forwarded. The capability of osteocytes in maintaining skeletal and mineral homeostasis is due to the fact that it acts as a mechano-sensor, able to transduce mechanical strains into biological signals and to trigger/modulate the bone remodeling, also because of the relevant role of sclerostin secreted by osteocytes, thus regulating different bone cell signaling pathways. The authors want to emphasize that the present review is centered on the morphological aspects of the osteocytes that clearly explain their functional implications and their role as bone orchestrators.
... The maintenance of normal bone structure is driven by the intercellular cross-talk that occurs among bone cells. As proposed by many authors (R. A. Dodds et al., 1993;Marotti and Palumbo, 2007;Skerry et al., 1989a,b) and largely demonstrated by Bonewald (2011) and Nakashima (Nakashima et al., 2011) osteocytes are considered the mechanosensors of bone (Bertacchini et al., 2017;Maycas et al., 2015;Nakashima et al., 2012) and are actively involved in orchestrating the function of both bone-forming osteoblasts and bone-resorbing osteoclasts. However, the role of osteocytes in osteoblast regulation, under both physiologic and pathologic conditions, is not fully characterized. ...
To develop durable bone healing strategies through improved control of bone repair, it is of critical importance to understand the mechanisms of bone mechanical integrity when in contact with biomaterials and implants. Bone mechanical integrity is defined here as the adaptation of structural properties of remodeled bone in regard to an applied mechanical loading. Accordingly, the authors present why future investigations in bone repair and regeneration should emphasize on the matrix surrounding the osteocytes. Osteocytes are mechanosensitive cells considered as the orchestrators of bone remodeling, which is the biological process involved in bone homeostasis. These bone cells are trapped in an interconnected porous network, the lacunocanalicular network, which is embedded in a bone mineralized extracellular matrix. As a consequence of an applied mechanical loading, the bone deformation results in the deformation of this lacunocanalicular network inducing a shift in interstitial fluid pressure and velocity, thus resulting in osteocyte stimulation. The material environment surrounding each osteocyte, the so called perilacunar and pericellular matrices properties, define its mechanosensitivity. While this mechanical stimulation pathway is well known, the laws used to predict bone remodeling are based on strains developing at a tissue scale, suggesting that these strains are related to the shift in fluid pressure and velocity at the lacunocanalicular scale. While this relationship has been validated through observation in healthy bone, the fluid behavior at the bone-implant interface is more complex. The presence of the implant modifies fluid behavior, so that for the same strain at a tissue scale, the shift in fluid pressure and velocity will be different than in a healthy bone tissue. In that context, new markers for bone mechanical integrity, considering fluid behavior, have to be defined. The viewpoint exposed by the authors indicates that the properties of the pericellular and the perilacunar matrices have to be systematically investigated and used as structural markers of fluid behavior in the course of bone biomaterial development.
