scholarly journals Enhancement of Osteoclastic Bone Resorption and Suppression of Osteoblastic Bone Formation in Response to Reduced Mechanical Stress Do Not Occur in the Absence of Osteopontin

2001 ◽  
Vol 193 (3) ◽  
pp. 399-404 ◽  
Author(s):  
Muneaki Ishijima ◽  
Susan R. Rittling ◽  
Teruhito Yamashita ◽  
Kunikazu Tsuji ◽  
Hisashi Kurosawa ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Mechanical Stress ◽  
Bone Matrix ◽  
Osteoclastic Bone Resorption ◽  
Tail Suspension ◽  
Wild Type ◽  
Osteoblastic Bone Formation

Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investigate the possible requirement for OPN in the transduction of mechanical signaling in bone metabolism in vivo, we examined the effect of unloading on the bones of OPN−/− mice using a tail suspension model. In contrast to the tail suspension–induced bone loss in wild-type mice, OPN−/− mice did not lose bone. Elevation of urinary deoxypyridinoline levels due to unloading was observed in wild-type but not in OPN−/− mice. Analysis of the mechanisms of OPN deficiency–dependent reduction in bone on the cellular basis resulted in two unexpected findings. First, osteoclasts, which were increased by unloading in wild-type mice, were not increased by tail suspension in OPN−/− mice. Second, measures of osteoblastic bone formation, which were decreased in wild-type mice by unloading, were not altered in OPN−/− mice. These observations indicate that the presence of OPN is a prerequisite for the activation of osteoclastic bone resorption and for the reduction in osteoblastic bone formation in unloaded mice. Thus, OPN is a molecule required for the bone loss induced by mechanical stress that regulates the functions of osteoblasts and osteoclasts.

scholarly journals Novel Osteogenic Factors derived from Functional Food: Role in Prevention of Osteoporosis

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Masayoshi Yamaguchi
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Functional Food ◽  
Human Subjects ◽  
Osteoclastic Bone Resorption ◽  
Bone Homeostasis ◽  
Osteoblastic Bone Formation ◽  
Prevention Of Osteoporosis ◽  
Osteogenic Effect

<p>Bone homeostasis is maintained through a delicate balance between osteoblastic bone formation and osteoclastic bone resorption. Bone loss is caused by decreasing in osteoblastic bone formation and increase in osteoclastic bone resorption, thereby leading to osteoporosis. Functional food factors may play a role in<br />the prevention of osteoporosis. Functional food factors including genistein, menaquinone-7 (vitamin K2) and β-cryptoxanthine have been shown to possess a potential osteogenic effect. These factors have been shown to reveal stimulatory effects on osteoblastic bone formation and suppressive effects on osteoclastic<br />bone resorption. Dietary intake of these factors has been shown to reveal preventive effects on bone loss in animal models of osteoporosis and human subjects. This review will introduce our findings concerning roles of functional food factors in regulation of bone homeostasis and prevention of osteoporosis.</p>

scholarly journals Osteopontin is required for mechanical stress-dependent signals to bone marrow cells

2007 ◽  
Vol 193 (2) ◽  
pp. 235-243 ◽  
Author(s):  
Muneaki Ishijima ◽  
Kunikazu Tsuji ◽  
Susan R Rittling ◽  
Teruhito Yamashita ◽  
Hisashi Kurosawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Loss ◽  
Mechanical Stress ◽  
Bone Marrow Cells ◽  
Bone Matrix ◽  
Nodule Formation ◽  
Tail Suspension ◽  
Wild Type ◽  
Marrow Cells

Mechanical stress to bone plays a crucial role in the maintenance of bone homeostasis. It causes the deformation of bone matrix and generates strain force, which could initiate the mechano-transduction pathway. The presence of osteopontin (OPN), which is one of the abundant proteins in bone matrix, is required for the effects of mechanical stress on bone, as we have reported that OPN-null (OPN−/−) mice showed resistance to unloading-induced bone loss. However, cellular mechanisms underlying the phenomenon have not been completely elucidated. To obtain further insight into the role of OPN in mediating mechanical stress effect on bone, we examined in vitro mineralization and osteoclast-like cell formation in bone marrow cells obtained from hind limb bones of OPN−/− mice after tail suspension. The levels of mineralized nodule formation of bone marrow cells derived from the femora subjected to unloading were decreased compared with that from loaded control in wild-type mice. However, these were not decreased in cells from OPN−/− mice after tail suspension compared with that from loaded OPN−/− mice. Moreover, while spreading of osteoclast-like cells derived from bone marrow cells of the femora subjected to unloading was enhanced compared with that from loaded control in wild-type mice, this enhancement of spreading of these cells derived from the femora subjected to unloading was not recognized compared with those from loaded control in OPN−/− mice. These data provided cellular bases for the effect of the OPN deficiency on in vitro reduced mineralized nodule formation by osteoblasts and on enhancement of osteoclast spreading in vitro induced by the absence of mechanical stress. These in vitro results correlate well with the resistance to unloading-induced bone loss in OPN−/− mice in vivo, suggesting that OPN has an important role in the effects of unloading-induced alterations of differentiation of bone marrow into osteoblasts and osteoclasts.

scholarly journals Free Fatty Acid Receptor 4 (GPR120) Stimulates Bone Formation and Suppresses Bone Resorption in the Presence of Elevated n-3 Fatty Acid Levels

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2621-2635 ◽  
Author(s):  
Seong Hee Ahn ◽  
Sook-Young Park ◽  
Ji-Eun Baek ◽  
Su-Youn Lee ◽  
Wook-Young Baek ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Free Fatty Acid Receptor

Free fatty acid receptor 4 (FFA4) has been reported to be a receptor for n-3 fatty acids (FAs). Although n-3 FAs are beneficial for bone health, a role of FFA4 in bone metabolism has been rarely investigated. We noted that FFA4 was more abundantly expressed in both mature osteoclasts and osteoblasts than their respective precursors and that it was activated by docosahexaenoic acid. FFA4 knockout (Ffar4−/−) and wild-type mice exhibited similar bone masses when fed a normal diet. Because fat-1 transgenic (fat-1Tg+) mice endogenously converting n-6 to n-3 FAs contain high n-3 FA levels, we crossed Ffar4−/− and fat-1Tg+ mice over two generations to generate four genotypes of mice littermates: Ffar4+/+;fat-1Tg−, Ffar4+/+;fat-1Tg+, Ffar4−/−;fat-1Tg−, and Ffar4−/−;fat-1Tg+. Female and male littermates were included in ovariectomy- and high-fat diet-induced bone loss models, respectively. Female fat-1Tg+ mice decreased bone loss after ovariectomy both by promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption than their wild-type littermates, only when they had the Ffar4+/+ background, but not the Ffar4−/− background. In a high-fat diet-fed model, male fat-1Tg+ mice had higher bone mass resulting from stimulated bone formation and reduced bone resorption than their wild-type littermates, only when they had the Ffar4+/+ background, but not the Ffar4−/− background. In vitro studies supported the role of FFA4 as n-3 FA receptor in bone metabolism. In conclusion, FFA4 is a dual-acting factor that increases osteoblastic bone formation and decreases osteoclastic bone resorption, suggesting that it may be an ideal target for modulating metabolic bone diseases.

Overexpression of Fam20C in osteoblast in vivo leads to increased cortical bone formation and osteoclastic bone resorption

Bone ◽  
2020 ◽  
Vol 138 ◽  
pp. 115414
Author(s):  
Katsutoshi Hirose ◽  
Takuya Ishimoto ◽  
Yu Usami ◽  
Sunao Sato ◽  
Kaori Oya ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Cortical Bone ◽  
Osteoclastic Bone Resorption

scholarly journals Autoinducer-2 and QseC Control Biofilm Formation and In Vivo Virulence of Aggregatibacter actinomycetemcomitans

2010 ◽  
Vol 78 (7) ◽  
pp. 2919-2926 ◽  
Author(s):  
Elizabeth A. Novak ◽  
HanJuan Shao ◽  
Carlo Amorin Daep ◽  
Donald R. Demuth
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Biofilm Formation ◽  
Alveolar Bone ◽  
Wild Type ◽  
Two Component System ◽  
Component System ◽  
Autoinducer 2 ◽  
Two Component

ABSTRACT Biofilm formation by the periodontal pathogen Aggregatibacter actinomycetemcomitans is dependent upon autoinducer-2 (AI-2)-mediated quorum sensing. However, the components that link the detection of the AI-2 signal to downstream gene expression have not been determined. One potential regulator is the QseBC two-component system, which is part of the AI-2-dependent response pathway that controls biofilm formation in Escherichia coli. Here we show that the expression of QseBC in A. actinomycetemcomitans is induced by AI-2 and that induction requires the AI-2 receptors, LsrB and/or RbsB. Additionally, inactivation of qseC resulted in reduced biofilm growth. Since the ability to grow in biofilms is essential for A. actinomycetemcomitans virulence, strains that were deficient in QseC or the AI-2 receptors were examined in an in vivo mouse model of periodontitis. The ΔqseC mutant induced significantly less alveolar bone resorption than the wild-type strain (P < 0.02). Bone loss in animals infected with the ΔqseC strain was similar to that in sham-infected animals. The ΔlsrB, ΔrbsB, and ΔlsrB ΔrbsB strains also induced significantly less alveolar bone resorption than the wild type (P < 0.03, P < 0.02, and P < 0.01, respectively). However, bone loss induced by a ΔluxS strain was indistinguishable from that induced by the wild type, suggesting that AI-2 produced by indigenous microflora in the murine oral cavity may complement the ΔluxS mutation. Together, these results suggest that the QseBC two-component system is part of the AI-2 regulon and may link the detection of AI-2 to the regulation of downstream cellular processes that are involved in biofilm formation and virulence of A. actinomycetemcomitans.

Erratum to “Overexpression of Fam20C in osteoblast in vivo leads to increased cortical bone formation and osteoclastic bone resorption” [Bone 138 (2020), 115414]

Bone ◽  
2021 ◽  
Vol 143 ◽  
pp. 115635
Author(s):  
Katsutoshi Hirose ◽  
Takuya Ishimoto ◽  
Yu Usami ◽  
Sunao Sato ◽  
Kaori Oya ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Cortical Bone ◽  
Osteoclastic Bone Resorption

scholarly journals Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

2011 ◽  
Vol 165 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Pierre J Marie ◽  
Moustapha Kassem
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Matrix ◽  
Bone Fragility ◽  
Osteoblastic Cell ◽  
Medline Search ◽  
Cell Functions ◽  
Age Related ◽  
Increased Risk

ObjectiveAge-related bone loss is associated with significant changes in bone remodeling characterized by decreased trabecular and periosteal bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Prevention or reversal of age-related decrease in bone mass and increase in bone fragility has been based on inhibition of bone resorption using anticatabolic drugs. The current challenge is to promote osteoblastogenesis and bone formation to prevent age-related bone deterioration.MethodsA limited number of approved therapeutic molecules are available to activate bone formation. Therefore, there is a need for anabolic drugs that promote bone matrix apposition at the endosteal, endocortical, and periosteal envelopes by increasing the number of osteoblast precursor cells and/or the function of mature osteoblasts. In this study, we review current therapeutics promoting bone formation and anabolic molecules targeting signaling pathways involved in osteoblastogenesis, based on selected full-text articles searched on Medline search from 1990 to 2010.Results and discussionWe present current therapeutic approaches focused on intermittent parathyroid hormone and Wnt signaling agonists/antagonists. We also discuss novel approaches for prevention and treatment of defective bone formation and bone loss associated with aging and osteoporosis. These strategies targeting osteoblastic cell functions may prove to be useful in promoting bone formation and improving bone strength in the aging population.

Irisin recouples osteogenesis and osteoclastogenesis to protect wear-particle-induced osteolysis by suppressing oxidative stress and RANKL production

2021 ◽  
Author(s):  
Sihan Hu ◽  
Yuan Xue ◽  
Jiachen He ◽  
Chichi Chen ◽  
Jie Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Resorption ◽  
Bone Formation ◽  
Wear Particle ◽  
Osteoclastic Bone Resorption ◽  
Bone Homeostasis ◽  
Periprosthetic Osteolysis ◽  
Osteoblastic Bone Formation

Disruption of bone homeostasis with the decrease of osteoblastic bone formation and the facilitated osteoclastic bone resorption is the leading cause of periprosthetic osteolysis. Accumulative studies indicate irisin has the...

scholarly journals Mechanical Loading Shows Anti-Myeloma Effects While Rescuing Bone Loss with Net Bone Formation in a Myeloma Bone Disease Murine Model

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3164-3164
Author(s):  
Fani Ziouti ◽  
Maximilian Rummler ◽  
Andreas Brandl ◽  
Andreas Beilhack ◽  
Maureen Lynch ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Remodeling ◽  
Mechanical Loading ◽  
Bone Disease ◽  
Whole Body ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mechanical Stimuli

Abstract Osteolytic bone disease (BD) is a hallmark of multiple myeloma (MM) with tumor cells in the bone marrow shifting the balance of the bone remodeling process towards massive bone resorption. As a result, patients develop devastating osteolytic lesions that lead to non-healing bone fractures and pain, affecting life quality and mortality rates. Bones have the capacity to adapt mass and structure to mechanical stimuli, as dramatically seen in young tennis athletes with muscle-bone asymmetries in the playing arm. We have previously shown that tibial mechanical loading rescued bone loss in our murine MOPC315.BM MM model with an advanced osteolytic phenotype. Here, we hypothesize that mechanical strain (1) modulates the bone microenvironment and (2) has antitumor activity in mice. (1) We determined bone formation and bone resorption parameters by time-lapsed microCT analysis to show how skeletal mechanical stimuli control MM bone disease (MMBD) progression over time. (2) To monitor tumor progression, we used non-invasive bioluminescence imaging (BLI) and enzyme-linked immunosorbent assay (ELISA) for detection of MOPC315.BM specific immunoglobulin A (IgA) levels. In our in vivo loading study, we injected MOPC315.BM cells intratibially (i.t.) in BALB/c mice to establish MMBD (n=17) and used PBS-injected (n=13) as well as noninjected mice (n=8) as controls. Eight (MM), seven (PBS) and 8 (noninjected) mice received compressive tibial loading for three weeks while nine (MM) and six (PBS) mice served as nonloaded controls. The bone remodeling response to mechanical loading was investigated by longitudinal in vivo microCT imaging performed every 5 days (at day 13, 18, 23, 28, and 33 after i.t. injection). MicroCT images from day 33 were geometrically registered onto images of day 13 and resampled into the same coordinate system using Amira and scripts written in Matlab for post-processing. Normalized newly mineralized and eroded bone volume (MV/BV, EV/BV), normalized formed and eroded bone surface area (MS/BS, ES/BS), mineralized thickness (MTh) and eroded depth (ED) were quantified. ANOVA was performed to examine the effect of loading and injection. Loading significantly increased the periosteal MV/BV, periosteal and endosteal MS/BS as well as decreased the periosteal EV/BV and periosteal and endocortical ES/BS. Endosteal MV/BV or EV/BV were not affected, which may be due to differences in the local strain environment at the two surfaces. In addition, mechanical stimuli did not influence ED, but led to diminished periosteal EV/BV and periosteal ES/BS suggesting fewer resorption sites in tibiae subjected to loading. Injection significantly affected periosteal and endosteal bone formation and resorption (Fig.1). Significant increases in cortical bone mass of loaded MM mice were accompanied by decreases in tumor load as evidenced by MOPC315.BM specific IgA levels (Fig. 2A). Interestingly, quantification of tibial and whole body bioluminescence signal intensities revealed controlled tumor growth in the loaded left tibia and a further delay of tumor cell dissemination throughout body of MM mice (Fig. 2B). Our data provide evidence that skeletal mechanical stimuli have anti-myeloma effects and rescue osteolytic bone loss in MMBD. The anabolic response to mechanical loads outweighs the anti-resorptive effect of MM cells, suggesting a combination of loading with bone resorption inhibitors in future therapeutic strategies. Disclosures No relevant conflicts of interest to declare.

Deficiency of CIZ, a nucleocytoplasmic shuttling protein, prevents unloading-induced bone loss through the enhancement of osteoblastic bone formation in vivo

Bone ◽  
2007 ◽  
Vol 40 (4) ◽  
pp. 852-860 ◽  
Author(s):  
K. Hino ◽  
T. Nakamoto ◽  
A. Nifuji ◽  
M. Morinobu ◽  
H. Yamamoto ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Nucleocytoplasmic Shuttling ◽  
Osteoblastic Bone Formation
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