scholarly journals The Influence of Radiation on Bone and Bone Cells—Differential Effects on Osteoclasts and Osteoblasts

2020 ◽  
Vol 21 (17) ◽  
pp. 6377
Author(s):  
Anna-Jasmina Donaubauer ◽  
Lisa Deloch ◽  
Ina Becker ◽  
Rainer Fietkau ◽  
Benjamin Frey ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Bone Cells ◽  
Positive Impact ◽  
Inflammatory Diseases ◽  
Future Research ◽  
Special Focus ◽  
Bone Homeostasis ◽  
Bone Microenvironment

The bone is a complex organ that is dependent on a tight regulation between bone formation by osteoblasts (OBs) and bone resorption by osteoclasts (OCs). These processes can be influenced by environmental factors such as ionizing radiation (IR). In cancer therapy, IR is applied in high doses, leading to detrimental effects on bone, whereas radiation therapy with low doses of IR is applied for chronic degenerative and inflammatory diseases, with a positive impact especially on bone homeostasis. Moreover, the effects of IR are of particular interest in space travel, as astronauts suffer from bone loss due to space radiation and microgravity. This review summarizes the current state of knowledge on the effects of IR on bone with a special focus on the influence on OCs and OBs, as these cells are essential in bone remodeling. In addition, the influence of IR on the bone microenvironment is discussed. In summary, the effects of IR on bone and bone remodeling cells strongly depend on the applied radiation dose, as differential results are provided from in vivo as well as in vitro studies with varying doses of IR. Furthermore, the isolated effects of IR on a single cell type are difficult to determine, as the bone cells and bone microenvironment are building a tightly regulated network, influencing on one another. Therefore, future research is necessary in order to elucidate the influence of different bone cells on the overall radiation-induced effects on bone.

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.

scholarly journals β2-Adrenergic Receptor Signaling in Osteoblasts Contributes to the Catabolic Effect of Glucocorticoids on Bone

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1412-1422 ◽  
Author(s):  
Yun Ma ◽  
Jeffry S. Nyman ◽  
Huan Tao ◽  
Heather H. Moss ◽  
Xiangli Yang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Cells ◽  
Sympathetic Nerves ◽  
Bone Diseases ◽  
Autonomic Nerves ◽  
High Dose ◽  
Bone Homeostasis ◽  
Adrenergic Stimulation

Abstract The sympathetic nervous system is a physiological regulator of bone homeostasis. Autonomic nerves are indeed present in bone, bone cells express the β2-adrenergic receptors (β2AR), and pharmacological or genetic disruption of sympathetic outflow to bone induces bone gain in rodents. These recent findings implied that conditions that affect β2AR signaling in osteoblasts and/or sympathetic drive to bone may contribute to bone diseases. In this study, we show that dexamethasone stimulates the expression of the β2AR in differentiated primary calvarial osteoblasts, as measured by an increase in Adrβ2 mRNA and β2AR protein level after short-term dexamethasone treatment. Isoproterenol-induced cAMP accumulation and the expression of the β2AR target gene Rankl were also significantly increased after dexamethasone pretreatment, indicating that dexamethasone promotes the responsiveness of differentiated osteoblasts to adrenergic stimulation. These in vitro results led to the hypothesis that glucocorticoid-induced bone loss, provoked by increased endogenous or high-dose exogenous glucocorticoids given for the treatment of inflammatory diseases, might, at least in part, be mediated by increased sensitivity of bone-forming cells to the tonic inhibitory effect of sympathetic nerves on bone formation or their stimulatory effect on bone resorption. Supporting this hypothesis, both pharmacological and genetic β2AR blockade in mice significantly reduced the bone catabolic effect of high-dose prednisolone in vivo. This study emphasizes the importance of sympathetic nerves in the regulation of bone homeostasis and indicates that this neuroskeletal signaling axis can be modulated by hormones or drugs and contribute to enhance pathological bone loss.

scholarly journals Fra-2/AP-1 controls bone formation by regulating osteoblast differentiation and collagen production

2010 ◽  
Vol 190 (6) ◽  
pp. 1093-1106 ◽  
Author(s):  
Aline Bozec ◽  
Latifa Bakiri ◽  
Maria Jimenez ◽  
Thorsten Schinke ◽  
Michael Amling ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Osteoblast Differentiation ◽  
Bone Cells ◽  
Activator Protein 1 ◽  
Bone Homeostasis ◽  
Newborn Mice ◽  
Important Regulator ◽  
Transcription Factor Complex

The activator protein-1 (AP-1) transcription factor complex, in particular the Fos proteins, is an important regulator of bone homeostasis. Fra-2 (Fosl2), a Fos-related protein of the AP-1 family, is expressed in bone cells, and newborn mice lacking Fra-2 exhibit defects in chondrocytes and osteoclasts. Here we show that Fra-2–deficient osteoblasts display a differentiation defect both in vivo and in vitro. Moreover, Fra-2–overexpressing mice are osteosclerotic because of increased differentiation of osteoblasts, which appears to be cell autonomous. Importantly, the osteoblast-specific osteocalcin (Oc) gene and collagen1α2 (col1α2) are transcriptional targets of Fra-2 in both murine and human bone cells. In addition, Fra-2, Oc, and col1 are expressed in stromal cells of human chondroblastic and osteoblastic osteosarcomas (Os’s) as well as during osteoblast differentiation of human Os cell lines. These findings reveal a novel function of Fra-2/AP-1 as a positive regulator of bone and matrix formation in mice and humans.

Increased Concentrations of Prostaglandin D2 During Post-Fracture Bone Remodeling

2010 ◽  
Vol 37 (3) ◽  
pp. 644-649 ◽  
Author(s):  
MAXIME A. GALLANT ◽  
ESTELLE CHAMOUX ◽  
MARTINE BISSON ◽  
CATARINA WOLSEN ◽  
JEAN-LUC PARENT ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Type I Collagen ◽  
Bone Cells ◽  
Bone Alkaline Phosphatase ◽  
Positive Influence ◽  
Fracture Repair ◽  
Prostaglandin D2 ◽  
Type I ◽  
Bone Homeostasis

Objective.To test the hypothesis that increased concentrations of prostaglandin D2 (PGD2) correlate with bone remodeling. Studies using isolated bone cells indicate that PGD2 may be implicated in the regulation of bone homeostasis, with a positive influence on bone anabolism. We studied patients with traumatic fractures and age- and sex-matched healthy controls as an in vivo model of increased bone remodeling.Methods.Thirty-five patients with bone fracture and matched controls were recruited. Urine and sera samples were collected. Urinary 11ß-PGF2α, a PGD2 metabolite, and PGE2 metabolites (PGEM), serum lipocalin-type PGD2 synthase (L-PGDS), bone alkaline phosphatase (bone ALP), and crosslinked C-telopeptides of type I collagen (CTX) were measured.Results.At 5–6 weeks post-fracture, 11ß-PGF2α, L-PGDS, bone ALP, and CTX were significantly increased in the fracture patients compared to controls. PGEM levels were not different between groups. Levels of 11ß-PGF2α and bone ALP were positively correlated, suggesting that PGD2 may be implicated in fracture repair.Conclusion.These results support our working hypothesis that PGD2 could be implicated in the control of bone anabolism in humans.

scholarly journals PKC-δ deficiency in B cells displays osteopenia accompanied with upregulation of RANKL expression and osteoclast–osteoblast uncoupling

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Shangfu Li ◽  
Qiuli Liu ◽  
Depeng Wu ◽  
Tianwei He ◽  
Jinbo Yuan ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Bone Structure ◽  
Bone Cells ◽  
Osteoclast Differentiation ◽  
Bone Homeostasis ◽  
Osteoblast Proliferation ◽  
And Function

Abstract PKC-δ is an important molecule for B-cell proliferation and tolerance. B cells have long been recognized to play a part in osteoimmunology and pathological bone loss. However, the role of B cells with PKC-δ deficiency in bone homeostasis and the underlying mechanisms are unknown. We generated mice with PKC-δ deletion selectively in B cells by crossing PKC-δ-loxP mice with CD19-Cre mice. We studied their bone phenotype using micro-CT and histology. Next, immune organs were obtained and analyzed. Western blotting was used to determine the RANKL/OPG ratio in vitro in B-cell cultures, ELISA assay and immunohistochemistry were used to analyze in vivo RANKL/OPG balance in serum and bone sections respectively. Finally, we utilized osteoclastogenesis to study osteoclast function via hydroxyapatite resorption assay, and isolated primary calvaria osteoblasts to investigate osteoblast proliferation and differentiation. We also investigated osteoclast and osteoblast biology in co-culture with B-cell supernatants. We found that mice with PKC-δ deficiency in B cells displayed an osteopenia phenotype in the trabecular and cortical compartment of long bones. In addition, PKC-δ deletion resulted in changes of trabecular bone structure in association with activation of osteoclast bone resorption and decrease in osteoblast parameters. As expected, inactivation of PKC-δ in B cells resulted in changes in spleen B-cell number, function, and distribution. Consistently, the RANKL/OPG ratio was elevated remarkably in B-cell culture, in the serum and in bone specimens after loss of PKC-δ in B cells. Finally, in vitro analysis revealed that PKC-δ ablation suppressed osteoclast differentiation and function but co-culture with B-cell supernatant reversed the suppression effect, as well as impaired osteoblast proliferation and function, indicative of osteoclast–osteoblast uncoupling. In conclusion, PKC-δ plays an important role in the interplay between B cells in the immune system and bone cells in the pathogenesis of bone lytic diseases.

scholarly journals Natural 3D-Printed Bioinks for Skin Regeneration and Wound Healing: A Systematic Review

Polymers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 1782 ◽  
Author(s):  
Ali Smandri ◽  
Abid Nordin ◽  
Ng Min Hwei ◽  
Kok-Yong Chin ◽  
Izhar Abd Aziz ◽  
...  
Keyword(s):  
Systematic Review ◽  
Wound Healing ◽  
Animal Studies ◽  
Positive Impact ◽  
Three Dimensional ◽  
Skin Regeneration ◽  
Future Research ◽  
Eligibility Criteria

Three-dimensional bioprinting has rapidly paralleled many biomedical applications and assisted in advancing the printing of complex human organs for a better therapeutic practice. The objective of this systematic review is to highlight evidence from the existing studies and evaluate the effectiveness of using natural-based bioinks in skin regeneration and wound healing. A comprehensive search of all relevant original articles was performed based on prespecified eligibility criteria. The search was carried out using PubMed, Web of Science, Scopus, Medline Ovid, and ScienceDirect. Eighteen articles fulfilled the inclusion and exclusion criteria. The animal studies included a total of 151 animals with wound defects. A variety of natural bioinks and skin living cells were implanted in vitro to give insight into the technique through different assessments and findings. Collagen and gelatin hydrogels were most commonly used as bioinks. The follow-up period ranged between one day and six weeks. The majority of animal studies reported that full wound closure was achieved after 2–4 weeks. The results of both in vitro cell culture and in vivo animal studies showed the positive impact of natural bioinks in promoting wound healing. Future research should be focused more on direct the bioprinting of skin wound treatments on animal models to open doors for human clinical trials.

scholarly journals Emerging Multifunctional Roles of Claudin Tight Junction Proteins in Bone

Endocrinology ◽  
2014 ◽  
Vol 155 (7) ◽  
pp. 2363-2376 ◽  
Author(s):  
Fatima. Z. Alshbool ◽  
Subburaman Mohan
Keyword(s):  
Tight Junction ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Osteoclast Differentiation ◽  
Cell Types ◽  
Future Research ◽  
Bone Homeostasis ◽  
Tight Junction Proteins ◽  
Regulation Of Expression ◽  
Junction Proteins

The imbalance between bone formation and resorption during bone remodeling has been documented to be a major factor in the pathogenesis of osteoporosis. Recent evidence suggests a significant role for the tight junction proteins, Claudins (Cldns), in the regulation of bone remodeling processes. In terms of function, whereas Cldns act “canonically” as key determinants of paracellular permeability, there is considerable recent evidence to suggest that Cldns also participate in cell signaling, ie, a “noncanonical function”. To this end, Cldns have been shown to regulate cell proliferation, differentiation, and gene expression in a variety of cell types. The present review will discuss Cldns’ structure, their expression profile, regulation of expression, and their canonical and non- canonical functions in general with special emphasis on bone cells. In order to shed light on the noncanonical functions of Cldns in bone, we will highlight the role of Cldn-18 in regulating bone resorption and osteoclast differentiation. Collectively, we hope to provide a framework for guiding future research on understanding how Cldns modulate osteoblast and osteoclast function and overall bone homeostasis. Such studies should provide valuable insights into the pathogenesis of osteoporosis, and may highlight Cldns as novel targets for the diagnosis and therapeutic management 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.

scholarly journals Cyclosporine A Promotes Bone Remodeling in LPS-Related Inflammation via Inhibiting ROS/ERK Signaling: Studies In Vivo and In Vitro

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Yuwei Zhao ◽  
Jing Gao ◽  
Yarong Zhang ◽  
Xueqi Gan ◽  
Haiyang Yu
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Bone Remodeling ◽  
Cyclosporine A ◽  
Alveolar Bone ◽  
Inflammatory Diseases ◽  
Bone Destruction ◽  
Erk Signaling

In some inflammatory diseases of bone, osteogenesis and osteoclasis are uncoupled and the balance is usually tipped resulting in bone destruction. The underlying mechanism of osteogenic dysfunction in inflammation still needs further study. This study is aimed at investigating the effects of cyclosporine A (CsA) on bone remodeling in lipopolysaccharide- (LPS-) related inflammation. In vivo, an alveolar bone defect model was established using 10-week-old C57BL/6J mice. The mice were divided into phosphate-buffered saline (PBS), LPS, and LPS+CsA groups. After 3 weeks, micro-CT analysis and histomorphometric evaluation were conducted. In vitro, murine osteoblasts were treated with vehicle medium, LPS, LPS+CsA, LPS+extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor (LPS+PD98059), and LPS+antioxidant (LPS+EUK134). Cell proliferation, osteogenic behaviors, oxidative stress, and ERK signaling were determined. By these approaches, LPS inhibited bone remodeling and promoted oxidative stress accumulation in alveolar bone defects. When animals were treated with CsA, all LPS-induced biochemical changes ameliorated with a marked protective effect. In vitro, the reactive oxygen species (ROS) levels in mitochondria increased in LPS-treated osteoblasts, with decreased expression of osteogenic differentiation genes. The CsA, PD98059, and EUK134 presented remarkable protective effects against LPS treatment. CsA effectively enhanced bone remodeling and attenuated oxidative stress caused by LPS via inhibiting ROS/ERK signaling. Taken together, the protective effect of CsA and the inhibitory effect of ERK signaling on the maintenance of mitochondrial function and reduction of ROS levels hold promise as a potential novel therapeutic strategy for inflammatory diseases in bones.

Lactoferrin in Bone Tissue Regeneration

2020 ◽  
Vol 27 (6) ◽  
pp. 838-853 ◽  
Author(s):  
Madalina Icriverzi ◽  
Valentina Dinca ◽  
Magdalena Moisei ◽  
Robert W. Evans ◽  
Mihaela Trif ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Cells ◽  
Bone Diseases ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Bone Tissue Regeneration ◽  
Bone Homeostasis ◽  
Active Compounds

: Among the multiple properties exhibited by lactoferrin (Lf), its involvement in bone regeneration processes is of great interest at the present time. A series of in vitro and in vivo studies have revealed the ability of Lf to promote survival, proliferation and differentiation of osteoblast cells and to inhibit bone resorption mediated by osteoclasts. Although the mechanism underlying the action of Lf in bone cells is still not fully elucidated, it has been shown that its mode of action leading to the survival of osteoblasts is complemented by its mitogenic effect. Activation of several signalling pathways and gene expression, in an LRPdependent or independent manner, has been identified. Unlike the effects on osteoblasts, the action on osteoclasts is different, with Lf leading to a total arrest of osteoclastogenesis. : Due to the positive effect of Lf on osteoblasts, the potential use of Lf alone or in combination with different biologically active compounds in bone tissue regeneration and the treatment of bone diseases is of great interest. Since the bioavailability of Lf in vivo is poor, a nanotechnology- based strategy to improve the biological properties of Lf was developed. The investigated formulations include incorporation of Lf into collagen membranes, gelatin hydrogel, liposomes, loading onto nanofibers, porous microspheres, or coating onto silica/titan based implants. Lf has also been coupled with other biologically active compounds such as biomimetic hydroxyapatite, in order to improve the efficacy of biomaterials used in the regulation of bone homeostasis. : This review aims to provide an up-to-date review of research on the involvement of Lf in bone growth and healing and on its use as a potential therapeutic factor in bone tissue regeneration.

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