Inhibition of RANKL-mediated bone remodeling decreases bone damage and improves strength in response to fatigue loading

2014 ◽  
Author(s):  
Nicolas Bonnet ◽  
Maude Gerbaix ◽  
Paul Kostenuik ◽  
Mike Ominsky ◽  
Serge Ferrari
Keyword(s):  
Bone Remodeling ◽  
Fatigue Loading ◽  
Bone Damage

scholarly journals Kinetics and Interplay of Mediators of Inflammation-Induced Bone Damage in the Course of Adjuvant Arthritis

2013 ◽  
Vol 26 (1) ◽  
pp. 37-48 ◽  
Author(s):  
S.M. Nanjundaiah ◽  
J.P. Stains ◽  
K.D. Moudgil
Keyword(s):  
Bone Remodeling ◽  
Inflammatory Cytokines ◽  
Adjuvant Arthritis ◽  
Bone Erosion ◽  
Experimental Conditions ◽  
Mediators Of Inflammation ◽  
Bone Damage ◽  
Tnf Α ◽  
Kinetics Of ◽  
Pro Inflammatory Cytokines

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, bone erosion, and cartilage destruction in the joints. It is increasingly being realized that inflammation might play an important role in inducing bone damage in arthritis. However, there is limited validation of this concept in vivo in well-controlled experimental conditions. We addressed this issue using the adjuvant arthritis (AA) model of RA. In AA, the draining lymph nodes are the main sites of activation of pathogenic leukocytes, which then migrate into the joints leading to the induction of arthritis. We tested the temporal kinetics of mediators of bone damage [e.g., receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and osteopontin (OPN)] and inflammation (pro-inflammatory cytokines and chemokines) in the draining lymph node cells (LNC) at different phases of AA, and then examined their inter-relationships. Our study revealed that, together with cytokines/chemokines, some of the mediators of bone remodeling are also produced in LNC. Various cytokines/chemokines showed distinct kinetics of expression as well as patterns of correlation with mediators of bone remodeling at different phases of the disease. Pro-inflammatory cytokines such as TNF-α are known to play an important role in bone damage. Interestingly, there was a positive correlation between TNF-α and RANKL, between RANKL and each of the 3 chemokines tested (RANTES, MIP-1α, and GRO/KC), and between TNF-α and RANTES. Our results in the AA model lend support to the concept of osteo-immune crosstalk during the course of autoimmune arthritis.

Bone Biology

2017 ◽  
Author(s):  
Elizabeth Weiss
Keyword(s):  
Trabecular Bone ◽  
Bone Remodeling ◽  
Calcium Homeostasis ◽  
Bone Biology ◽  
Diarthrodial Joint ◽  
Bone Damage ◽  
Bone Changes ◽  
Cartilage Cells ◽  
Wolff’S Law ◽  
Haversian System

This chapter introduces readers to the basics of understanding bone’s functions, which include calcium homeostasis and enabling movement, bone’s components, such as the collagen, and bone’s organization, such as the Haversian system found in cortical bone. The focus of this chapter is on explaining concepts of bone remodeling, which is thought to prevent fractures and other bone damage, and repair, which can take place at macro-levels and micro-levels. Wolff’s Law of bone remodeling, which was initially focused on trabecular bone changes, is discussed in terms of bone’s response to forces that result in strains and stresses. Finally, diarthrodial joint remodeling and repair are discussed; cartilage cells were once thought to be static, yet now they are known to also respond to stresses.

Bone Remodeling Algorithm Incorporating Various Quantities as Mechanical Stimulus and Assuming Initial Microcrack in Bone

2017 ◽  
Vol 754 ◽  
pp. 189-193
Author(s):  
Libor Borák ◽  
Petr Marcián
Keyword(s):  
Finite Element ◽  
Bone Resorption ◽  
Energy Density ◽  
Bone Remodeling ◽  
Material Properties ◽  
Strain Energy Density ◽  
Strain Energy ◽  
Mechanical Stimulus ◽  
Coupled Processes ◽  
Bone Damage

It is widely accepted that bones have the ability to adapt to new biomechanical environment by changing their material properties, geometry and inner architecture. Bones have also an exceptional ability to self-repair, to remove microcracks and to prevent the bone damage caused by the fatigue failure. These abilities are enabled through coupled processes of bone resorption and bone formation, the processes collectively referred to as bone remodeling. Numerous studies have shown that bone remodeling is governed by combination of mechanical stimulus (strains) and its frequency, both sensed by sensor cells (osteocytes). Through mechanotransduction, the stimulus is transmitted to actor cells (osteoclasts, osteoblasts) that actually do the bone resorption or formation. Several theories have been proposed to predict bone remodeling and several finite-element-based algorithms have been introduced. The vast majority of them uses strain energy density as the mechanical stimulus. The purpose of this paper is to investigate and discuss the applicability of also other strain-based representations of the mechanical stimulus in simulations of remodeling of bone with an initial microcrack. The need for developing more reliable models is essential for both clinicians and engineers who are interested, for instance, in prediction of bone performance when various implants are involved.

scholarly journals Bone Remodeling Model Integrating the Biological Function and Damage Influences for the Cortical-Trabecular Interface

2021 ◽  
Vol 9 ◽  
Author(s):  
Imed SOLTANI ◽  
◽  
Imane AIT OUMGHAR ◽  
Abdelwahed BARKAOUI ◽  
Tarek LAZGHAB ◽  
...  
Keyword(s):  
Bone Density ◽  
Bone Remodeling ◽  
Volume Fraction ◽  
Research Work ◽  
Bone Volume ◽  
Bone Volume Fraction ◽  
Saturation Zone ◽  
Damage Repair ◽  
Bone Damage ◽  
Over Time

Bone remodeling process has been widely investigated in literature from an experimental and theoretical viewpoint. Indeed, the biological process of bone remodeling allows a continuous renewal of the microstructure over time and thus, it contributes to decrease the bone damage by repairing it. This research work aims to study the biological function’s (fbio) effects on the bone remodeling process trough bone density evolution. Parameter fbio is one of the important parameters that controls bone volume variation. The biological bone remodeling process is modeled in terms of equations describing the activity of the Basic Multi-cellular Units (BMU). We use a mathematical model to simulate damage repair, based on Garcia Aznar’s model. The results of simulation show a good match with experimental and clinical data: bone porosity decreases over time and decreases also as the biological factors increase. In the same view, the apparent density (ρa) decreases with bone volume fraction increases. We note that the governance of the evolution of bone density leads to consider the evolution of bone volume during youthful and the maturation phase with their saturation zone for adult in terms of growth.

scholarly journals Chinese Herbal Formula Huo-Luo-Xiao-Ling Dan Protects against Bone Damage in Adjuvant Arthritis by Modulating the Mediators of Bone Remodeling

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Siddaraju M. Nanjundaiah ◽  
David Y.-W. Lee ◽  
Brian M. Berman ◽  
Kamal D. Moudgil
Keyword(s):  
Bone Remodeling ◽  
Adjuvant Arthritis ◽  
Cartilage Damage ◽  
Effective Management ◽  
Promising Alternative ◽  
Adjunct Treatment ◽  
Chinese Herbal Formula ◽  
Chinese Herbal ◽  
Bone Damage ◽  
Receptor Activator

Huo-luo-xiao-ling dan (HLXL) is an herbal mixture that has long been used in traditional Chinese medicine for the treatment of rheumatoid arthritis (RA) and other inflammatory disorders. Despite the availability of potent conventionally used drugs for RA, their limited efficacy in a proportion of patients coupled with their high cost and severe adverse effects has necessitated the search for novel therapeutics for this debilitating disease. Further, the control of both inflammation and bone damage is essential for effective management of arthritis. The aim of our study was to evaluate the efficacy of HLXL against arthritic bone damage in adjuvant arthritis (AA) model of RA. Our results show that HLXL treatment suppressed inflammatory arthritis and reduced bone and cartilage damage in the joints of arthritic Lewis rats. HLXL-induced protection against bone damage was mediated primarily via inhibition of mediators of osteoclastic bone remodeling (e.g., receptor activator of nuclear factor kappa-B ligand; RANKL), skewing of RANKL/osteoprotegerin (OPG) ratio in favor of antiosteoclastic activity, reduction in the number of osteoclasts in the arthrodial joint's bone, and inhibition of cytokine production and MMP activity. Our results suggest that HLXL might offer a promising alternative/adjunct treatment for both inflammation and bone damage in RA.

scholarly journals Binge Alcohol-Induced Bone Damage is Accompanied by Differential Expression of Bone Remodeling-Related Genes in Rat Vertebral Bone

2009 ◽  
Vol 84 (6) ◽  
pp. 474-484 ◽  
Author(s):  
John J. Callaci ◽  
Ryan Himes ◽  
Kristen Lauing ◽  
Frederick H. Wezeman ◽  
Kirstyn Brownson
Keyword(s):  
Differential Expression ◽  
Bone Remodeling ◽  
Vertebral Bone ◽  
Bone Damage

scholarly journals Periostin Deficiency Increases Bone Damage and Impairs Injury Response to Fatigue Loading in Adult Mice

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e78347 ◽  
Author(s):  
Nicolas Bonnet ◽  
Evelyne Gineyts ◽  
Patrick Ammann ◽  
Simon J. Conway ◽  
Patrick Garnero ◽  
...  
Keyword(s):  
Fatigue Loading ◽  
Injury Response ◽  
Adult Mice ◽  
Bone Damage

scholarly journals B cell autoimmunity and bone damage in rheumatoid arthritis

Reumatismo ◽  
2016 ◽  
Vol 68 (3) ◽  
pp. 117 ◽  
Author(s):  
S. Bugatti ◽  
L. Bogliolo ◽  
C. Montecucco ◽  
A. Manzo
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Bone Remodeling ◽  
Mechanistic Explanation ◽  
Multiple Roles ◽  
Persistent Inflammation ◽  
Bone Damage ◽  
Substantial Progress ◽  
Citrullinated Protein ◽  
Made In

Rheumatoid arthritis (RA) is a chronic immune-inflammatory disease associated with significant bone damage. Pathological bone remodeling in RA is primarily driven by persistent inflammation. Indeed, pro-inflammatory cytokines stimulate the differentiation of bone-resorbing osteoclasts and, in parallel, suppress osteoblast function, resulting in net loss of bone. Abating disease activity thus remains the major goal of any treatment strategy in patients with RA. Autoantibody-positive patients, however, often show a rapidly progressive destructive course of the disease, disproportionate to the level of inflammation. The epidemiological association between RA-specific autoantibodies, in particular anti-citrullinated protein autoantibodies, and poor structural outcomes has recently found mechanistic explanation in the multiple roles that B cells play in bone remodeling. In this review, we will summarize the substantial progress that has been made in deciphering how B cells and autoantibodies negatively impact on bone in the course of RA, through both inflammation-dependent and independent mechanisms.

scholarly journals Non-invasive imaging demonstrates clinical features of ankylosing spondylitis in a rat adjuvant model: a case study

2016 ◽  
Author(s):  
N. Accart ◽  
J. Dawson ◽  
F. Kolbinger ◽  
I. Kramer ◽  
N. Beckmann
Keyword(s):  
Ankylosing Spondylitis ◽  
Bone Remodeling ◽  
Drug Testing ◽  
Soft Tissues ◽  
Experimental Period ◽  
Micro Ct ◽  
Non Invasive ◽  
Spine Imaging ◽  
Bone Damage

Ankylosing spondylitis is a common rheumatic disease involving both inflammatory erosive osteopenia and bony overgrowth. Main disease features are recapitulated in small rodents challenged with complete Freund’s adjuvant. MRI was used to follow longitudinally in vivo changes induced in the rat spine and micro-CT as terminal assessment of bone damage. Histochemistry methods were used to validate these imaging modalities in view of preclinical drug testing and translational applications of spine imaging. Animals were examined using a 3D fat-suppressed gradient-echo sequence, following the injection of gadolinium. At the end of the study, spines were excised for micro-CT and histological examination. Signals reflecting inflammation were detected at levels L5-L6 of the lumbar spine throughout the experimental period, peaking at day 27 after adjuvant. At day 14 the inflammatory response occurred along ligaments but it expanded to nearby soft tissues at later time points. From day 27 onwards inflammation was also detected within the bone, in areas where erosion occurred, and bone-like structures were formed. Micro-CT showed bone remodeling. Histology of isolated spines confirmed the inflammation and bone remodeling observed in vivo. The present study including three complementary approaches clearly demonstrates the potential of imaging for longitudinal assessments of changes in the spine in this animal model in view of preclinical pharmacological studies. The excellent correlation seen between the in vivo images and the histology underlines its fundamental role in the validation of non-invasive imaging readouts.

Does short-term administration of glucagon-like peptide type 2 affect bone mass and markers of bone remodeling in short bowel patients?

2001 ◽  
Vol 120 (5) ◽  
pp. A314-A314
Author(s):  
K HADERSLEV ◽  
P JEPPESEN ◽  
B HARTMANN ◽  
J THULESEN ◽  
J GRAFF ◽  
...  
Keyword(s):  
Bone Mass ◽  
Bone Remodeling ◽  
Short Term ◽  
Short Bowel ◽  
Term Administration ◽  
Glucagon Like Peptide
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