Tissue Strain Transduction and Amplification at the Osteocyte as a Result of Microstructural Changes in the Bone Matrix

2007 ◽  
Author(s):  
Amber Rath Bonivtch ◽  
Lynda F. Bonewald ◽  
Daniel P. Nicolella
Keyword(s):  
Bone Cells ◽  
Bone Matrix ◽  
Mechanical Strain ◽  
Bone Cell ◽  
Cellular Level ◽  
Tissue Strain ◽  
Biological Responses ◽  
Spatial Level

It is well known that bone adapts to changes in its mechanical environment and that this adaptation is controlled at the cellular level through the coordinated actions of osteoblasts, osteocytes, and osteoclasts. Osteocytes make up over 90% of all bone cells [1], and are hypothesized to be the mechanosensors in bone [2] that mediate the effects of bone loading through their extensive communication network. The application of force to the skeletal system produces several potential stimuli for osteocyte function including hydrostatic pressure, fluid flow-induced shear stress, and bone tissue strain. Previously, the basis used for studying the stimulatory effects of mechanical strain on bone cell biological responses in vitro has been the direct measurement of bone strain in humans during various physical activities [3,4]. The limitation of applying this strain magnitude data to cells in vitro, however, is that the in vivo strain gage measurements represent continuum measures of bone deformation. Clearly, at the spatial level of bone cells, cortical bone is not a continuum and microstructural inhomogeneities will result in inhomogeneous microstructural strain fields; local tissue strains will be magnified in association with microstructural features [5,6]. It is unclear as to how much of these magnified strains will be directly transmitted to the osteocyte itself. Additionally, if the osteocyte has the ability to alter its perilacunar environment [7], it is unknown what effect do these changes have on the strain that is transmitted to the osteocyte and cell process.

scholarly journals Protocol of Co-Culture of Human Osteoblasts and Osteoclasts to Test Biomaterials for Bone Tissue Engineering

2022 ◽  
Vol 5 (1) ◽  
pp. 8
Author(s):  
Giorgia Borciani ◽  
Giorgia Montalbano ◽  
Nicola Baldini ◽  
Chiara Vitale-Brovarone ◽  
Gabriela Ciapetti
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Bone Cells ◽  
Bone Cell ◽  
Seeding Density ◽  
Bone Homeostasis ◽  
Bone Microenvironment

New biomaterials and scaffolds for bone tissue engineering (BTE) applications require to be tested in a bone microenvironment reliable model. On this assumption, the in vitro laboratory protocols with bone cells represent worthy experimental systems improving our knowledge about bone homeostasis, reducing the costs of experimentation. To this day, several models of the bone microenvironment are reported in the literature, but few delineate a protocol for testing new biomaterials using bone cells. Herein we propose a clear protocol to set up an indirect co-culture system of human-derived osteoblasts and osteoclast precursors, providing well-defined criteria such as the cell seeding density, cell:cell ratio, the culture medium, and the proofs of differentiation. The material to be tested may be easily introduced in the system and the cell response analyzed. The physical separation of osteoblasts and osteoclasts allows distinguishing the effects of the material onto the two cell types and to evaluate the correlation between material and cell behavior, cell morphology, and adhesion. The whole protocol requires about 4 to 6 weeks with an intermediate level of expertise. The system is an in vitro model of the bone remodeling system useful in testing innovative materials for bone regeneration, and potentially exploitable in different application fields. The use of human primary cells represents a close replica of the bone cell cooperation in vivo and may be employed as a feasible system to test materials and scaffolds for bone substitution and regeneration.

Control of Oriented Extracellular Matrix Similar to Anisotropic Bone Microstructure

2014 ◽  
Vol 783-786 ◽  
pp. 72-77 ◽  
Author(s):  
Takayoshi Nakano ◽  
Aira Matsugaki ◽  
Takuya Ishimoto ◽  
Mitsuharu Todai ◽  
Ai Serizawa ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Bone Tissue ◽  
Bone Cells ◽  
Crystal Surface ◽  
Early Stage ◽  
Bone Microstructure ◽  
Bone Cell ◽  
Collagen Fibers

Bone microstructure is dominantly composed of anisotropic extracellular matrix (ECM) in which collagen fibers and epitaxially-oriented biological apatite (BAp) crystals are preferentially aligned depending on the bone anatomical position, resulting in exerting appropriate mechanical function. The regenerative bone in bony defects is however produced without the preferential alignment of collagen fibers and the c-axis of BAp crystals, and subsequently reproduced to recover toward intact alignment. Thus, it is necessary to produce the anisotropic bone-mimetic tissue for the quick recovery of original bone tissue and the related mechanical ability in the early stage of bone regeneration. Our group is focusing on the methodology for regulating the arrangement of bone cells, the following secretion of collagen and the self-assembled mineralization by oriented BAp crystallites. Cyclic stretching in vitro to bone cells, principal-stress loading in vivo on scaffolds, step formation by slip traces on Ti single crystal, surface modification by laser induced periodic surface structure (LIPSS), anisotropic collagen substrate with the different degree of orientation, etc. can dominate bone cell arrangement and lead to the construction of the oriented ECM similar to the bone tissue architecture. This suggests that stress/strain loading, surface topography and chemical anisotropy are useful to produce bone-like microstructure in order to promote the regeneration of anisotropic bone tissue and to understand the controlling parameters for anisotropic osteogenesis induction.

scholarly journals Increased serum and bone matrix levels of transforming growth factor β1 in patients with GH deficiency in response to GH treatment

2011 ◽  
Vol 165 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Thor Ueland ◽  
Tove Lekva ◽  
Kari Otterdal ◽  
Tuva B Dahl ◽  
Nicoleta Cristina Olarescu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cortical Bone ◽  
Transforming Growth Factor ◽  
Bone Cells ◽  
Gh Deficiency ◽  
Bone Matrix ◽  
Transforming Growth Factor Β1 ◽  
Gh Treatment

ObjectivePatients with adult onset GH deficiency (aoGHD) have secondary osteoporosis, which is reversed by long-term GH substitution. Transforming growth factor β1 (TGFβ1 or TGFB1) is abundant in bone tissue and could mediate some effects of GH/IGFs on bone. We investigated its regulation by GH/IGF1in vivoandin vitro.Design and methodsThe effects of GH substitution (9–12 months, placebo controlled) on circulating and cortical bone matrix contents of TGFβ1 were investigated in patients with aoGHD. The effects of GH/IGF1 on TGFβ1 secretion in osteoblasts (hFOB), adipocytes, and THP-1 macrophages as well as the effects on release from platelets were investigatedin vitro.ResultsIn vivoGH substitution increased TGFβ1 protein levels in cortical bone and serum.In vitro, GH/IGF1 stimulation induced a significant increase in TGFβ1 secretion in hFOB. In contrast, no major effect of GH/IGF1 on TGFβ1 was found in adipocytes and THP-1 macrophages. Finally, a minor modifying effect on SFLLRN-stimulated platelet release of TGFβ1 was observed in the presence of IGF1.ConclusionGH substitution increases TGFβ1in vivoandin vitro, and this effect could contribute to improved bone metabolism during such therapy, potentially reflecting direct effect of GH/IGF1 on bone cells.

Polycaprolactone/hydroxyapatite composite scaffolds: Preparation, characterization, and in vitro and in vivo biological responses of human primary bone cells

2010 ◽  
Vol 94A (1) ◽  
pp. 241-251 ◽  
Author(s):  
Boontharika Chuenjitkuntaworn ◽  
Wipawan Inrung ◽  
Damrong Damrongsri ◽  
Kongkwan Mekaapiruk ◽  
Pitt Supaphol ◽  
...  
Keyword(s):  
Bone Cells ◽  
Composite Scaffolds ◽  
Biological Responses ◽  
Hydroxyapatite Composite ◽  
Primary Bone

scholarly journals Synergic effects of decellularized bone matrix, hydroxyapatite, and extracellular vesicles on repairing of the rabbit mandibular bone defect model

2020 ◽  
Author(s):  
Asrin Emami ◽  
Tahereh Talaei-Khozani ◽  
Saeid Tavanafar ◽  
Nehleh Zareifard ◽  
Negar Azarpira ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Extracellular Vesicles ◽  
Bone Repair ◽  
Bone Matrix ◽  
Bone Cell ◽  
Histochemical Staining ◽  
Beneficial Effects ◽  
Mg63 Cells

Abstract Background: Extracellular vesicles (ECV) and bone extracellular matrix (ECM) have beneficial effects on the treatment of some pathological conditions. The purpose of this study was to find the synergic effects of decellularized bone (DB) ECM and ECVs on the repair of rabbit. Methods: The quality of decellularized sheep bones was confirmed by H&E, Hoechst, DNA quantification, immunohistochemistry, histochemical staining, and scanning electron microscopy (SEM). Osteoblast-derived ECVs were evaluated by internalization test, Transmission electron microscopy, Dynamic light scattering, and flow cytometry for CD9, CD63, CD81 markers. The hydrogel containing DB and hydroxyapatite (HA) with or without ECVs was evaluated for osteoblast functions and bone repair both in vitro and in vivo. Results: The data indicated ECM preservation after decellularization as well as cell depletion. In vitro assessments revealed that mineralization and alkaline phosphatase activity did not improve after treatment of MG63 cells by ECVs, while in vivo morphomatrical estimations showed synergic effects of ECVs and DB+HA hydrogels on increasing the number of bone-specific cells and vessel and bone area compared to the control, DB+HA and ECV-treated groups. Conclusions: The DB enriched with ECVs can be an ideal scaffold for bone tissue engineering and may provide a suitable niche for bone cell migration and differentiation.

Physiological Levels of Substrate Deformation Are Less Stimulatory to Bone Cells Compared to Fluid Flow

1999 ◽  
Author(s):  
Jun You ◽  
Clare E. Yellowley ◽  
Henry J. Donahue ◽  
Christopher R. Jacobs
Keyword(s):  
Fluid Flow ◽  
Matrix Protein ◽  
Bone Cells ◽  
Bone Matrix ◽  
Biological Response ◽  
Bone Cell ◽  
Osteoblastic Cells ◽  
Physiological Strain ◽  
Substrate Strain

Abstract It is believed that bone cells can sense mechanical loading and alter bone external shape and internal structure to efficiently support the load bearing demands placed upon it. However, the mechanism by which bone cells sense and respond to their mechanical environment is still poorly understood. In particular, the load-induced signals to which bone cells respond, e.g. fluid flow, substrate deformation, electrokinetic effects etc., are unclear. Furthermore, there are few studies focused on the effects of physiological strain (strain < 0.5%, Burr, 1996; Owan, 1997) on bone cells. The goal of this study was to investigate cytosolic Ca2+ mobilization (a very early signaling event) in response to different substrate strains (physiological or supra-physiological strains), and to distinguish the effects of substrate strain from those of fluid flow by applying precisely controlled strain without induced fluid flow. In addition, we quantified the effect of physiologically relevant fluid flow (Cowin, 1995) and substrate stretch on the expression of mRNA for the bone matrix protein osteopontin (OPN). A computer controlled stretch device was employed to apply different substrate strains, 0.1%, 1%, 5% and 10%. A parallel plate flow chamber was used to test cell responses to steady and oscillating flows (20dyn/cm2, 1Hz). Our data demonstrate that physiological strain (< 0.5%) does not induce [Ca2+]i responses in primary rat osteoblastic cells (ROB) in vitro. However, there was a significant (p < 0.05) increase in the number of responding cells at supra-physiological strains of 1, 5, and 10% suggesting that the cells were capable of a biological response. Similar results for human fetal osteoblastic cells (hFOB 1.19) and osteocyte-like cells (ML0-Y4) were obtained. Furthermore, compared to physiological substrate deformation, physiological fluid flow induced greater [Ca2+]i responses for hFOB cells, and these [Ca2+]i responses were quantitatively similar to those obtained for 10% substrate strain. Moreover we found no change in osteopontin mRNA expression after 0.5% strain stretch. Conversely, physiological oscillating flow (20dyn/cm2, 1Hz) caused a significant increase in osteopontin mRNA. These data suggest that, relative to fluid flow, substrate deformation may play less of a role in bone cell mechanotransduction.

scholarly journals Synergic effects of decellularized bone matrix, hydroxyapatite, and extracellular vesicles on repairing of the rabbit mandibular bone defect model

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Asrin Emami ◽  
Tahereh Talaei-Khozani ◽  
Saeid Tavanafar ◽  
Nehleh Zareifard ◽  
Negar Azarpira ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Extracellular Vesicles ◽  
Bone Repair ◽  
Bone Matrix ◽  
Bone Cell ◽  
Histochemical Staining ◽  
Beneficial Effects ◽  
Mg63 Cells

Abstract Background Extracellular vesicles (ECV) and bone extracellular matrix (ECM) have beneficial effects on the treatment of some pathological conditions. The purpose of this study was to find the synergic effects of decellularized bone (DB) ECM and ECVs on the repair of rabbit. Methods The quality of decellularized sheep bones was confirmed by H&E, Hoechst, DNA quantification, immunohistochemistry, histochemical staining, and scanning electron microscopy (SEM). Osteoblast-derived ECVs were evaluated by internalization test, Transmission electron microscopy, Dynamic light scattering, and flow cytometry for CD9, CD63, CD81 markers. The hydrogel containing DB and hydroxyapatite (HA) with or without ECVs was evaluated for osteoblast functions and bone repair both in vitro and in vivo. Results The data indicated ECM preservation after decellularization as well as cell depletion. In vitro assessments revealed that mineralization and alkaline phosphatase activity did not improve after treatment of MG63 cells by ECVs, while in vivo morphomatrical estimations showed synergic effects of ECVs and DB + HA hydrogels on increasing the number of bone-specific cells and vessel and bone area compared to the control, DB + HA and ECV-treated groups. Conclusions The DB enriched with ECVs can be an ideal scaffold for bone tissue engineering and may provide a suitable niche for bone cell migration and differentiation.

scholarly journals Review on material parameters to enhance bone cell function in vitro and in vivo

2020 ◽  
Vol 48 (5) ◽  
pp. 2039-2050
Author(s):  
Eric Madsen ◽  
Merjem Mededovic ◽  
David H. Kohn
Keyword(s):  
Cell Function ◽  
Bone Cells ◽  
Bone Cell ◽  
Bone Augmentation ◽  
Material Parameters ◽  
Specific Material ◽  
Resorbable Implants ◽  
Resorbable Materials

Bone plays critical roles in support, protection, movement, and metabolism. Although bone has an innate capacity for regeneration, this capacity is limited, and many bone injuries and diseases require intervention. Biomaterials are a critical component of many treatments to restore bone function and include non-resorbable implants to augment bone and resorbable materials to guide regeneration. Biomaterials can vary considerably in their biocompatibility and bioactivity, which are functions of specific material parameters. The success of biomaterials in bone augmentation and regeneration is based on their effects on the function of bone cells. Such functions include adhesion, migration, inflammation, proliferation, communication, differentiation, resorption, and vascularization. This review will focus on how different material parameters can enhance bone cell function both in vitro and in vivo.

From Mouse to Man: Redefining the Role of Insulin-Like Growth Factor-I in the Acquisition of Bone Mass

2003 ◽  
Vol 228 (3) ◽  
pp. 245-252 ◽  
Author(s):  
Shoshana Yakar ◽  
Clifford J. Rosen
Keyword(s):  
Growth Factor ◽  
Cell Function ◽  
Bone Cells ◽  
Bone Cell ◽  
Insulin Like Growth Factor ◽  
In Vivo Models ◽  
Igf I

The insulin-like growth factor system (IGF) has been linked to the process of bone acquisition through epidemiologic analyses of large cohorts and in vitro studies of bone cells. But the exact relationship between expression of IGF-I in bone and skeletal homeostasis or pathologic conditions, such as osteoporosis, remains poorly defined. Recent advances in genomic engineering have resulted in the development of better in vivo models to test the role of IGF-I during development and maintenance of the adult skeleton. It is now established that skeletal expression of IGF-I is critical for differentiative bone cell function. It may also be essential for the full anabolic effects of parathyroid hormone on trabecular bone and for some component of biomineralization. Evidence from conditional mutagenesis studies suggests that serum IGF-I may represent more than a storage depot or permissive factor during the final phase of skeletal acquisition. This work re-examines the original tenets of the “somatomedin hypothesis” in light of these newer mouse models and their remarkable skeletal phenotypes. The implications are far reaching and suggest that newer approaches for manipulating the IGF regulatory system may one day be useful as therapeutic adjuncts for the treatment of osteoporosis.

Megakaryocyte-driven changes in bone health: lessons from mouse models of myelofibrosis and related disorders

2021 ◽  
Author(s):  
Mariya Stavnichuk ◽  
Svetlana V. Komarova
Keyword(s):  
Bone Marrow ◽  
Mouse Models ◽  
Cell Function ◽  
Bone Cells ◽  
Bone Marrow Cells ◽  
Bone Cell ◽  
Bone Architecture ◽  
Bone Homeostasis

Over the years, numerous studies demonstrated reciprocal communications between processes of bone marrow hematopoiesis and bone remodeling. Megakaryocytes, rare bone marrow cells responsible for platelet production, were demonstrated to be involved in bone homeostasis. Myelofibrosis, characterized by an increase in pleomorphic megakaryocytes in the bone marrow, commonly leads to the development of osteosclerosis. In vivo, an increase in megakaryocyte number was shown to result in osteosclerosis in GATA-1low, NF-E2-/-, TPOhigh, Mpllf/f;PF4cre, Lnk-/-, Mpig6b-/-, Mpig6bfl/fl;Gp1ba-Cr+/KI, Pt-vWD mouse models. In vitro, megakaryocytes stimulate osteoblast proliferation and have variable effects on osteoclast proliferation and activity through soluble factors and direct cell-cell communications. Intriguingly, new studies revealed that the ability of megakaryocytes to communicate with bone cells is affected by the age and sex of animals. This mini-review summarises changes seen in bone architecture and bone cell function in mouse models with an elevated number of megakaryocytes and the effects megakaryocytes have on osteoblasts and osteoclasts in vitro, and discusses potential molecular players that can mediate these effects.

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