Skeletal maturation substantially affects elastic tissue properties in the endosteal and periosteal regions of loaded mice tibiae

Checa, Sara; Hesse, Bernhard; Roschger, Paul; Aido, Marta; Duda, Georg N.; Raum, Kay; Willie, Bettina M.

doi:10.1016/j.actbio.2015.04.020

Cited by 10 publications

(5 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, both Raman spectroscopy and RPI analyses are performed at the bone surface where new bone has been repeatedly found after axial loading [16, 17, 25, 36], indicating that we are indeed mainly studying the quality of the newly formed bone. Previous studies have shown that short-term loading only alters the chemical properties of new periosteal and endosteal modeled bone, and not the old intracortical bone, in response to load [19, 42], further indicating that the changes in bone chemistry that we see in response to loading are mainly due to the newly formed bone and not alterations in the old intracortical bone.…”

Section: Discussionsupporting

confidence: 58%

Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone

et al. 2016

View full text Add to dashboard Cite

SummaryLoading increases bone mass and strength in a site-specific manner; however, possible effects of loading on bone matrix composition have not been evaluated. Site-specific structural and material properties of mouse bone were analyzed on the macro- and micro/molecular scale in the presence and absence of axial loading. The response of bone to load is heterogeneous, adapting at molecular, micro-, and macro-levels.IntroductionOsteoporosis is a degenerative disease resulting in reduced bone mineral density, structure, and strength. The overall aim was to explore the hypothesis that changes in loading environment result in site-specific adaptations at molecular/micro- and macro-scale in mouse bone.MethodsRight tibiae of adult mice were subjected to well-defined cyclic axial loading for 2 weeks; left tibiae were used as physiologically loaded controls. The bones were analyzed with μCT (structure), reference point indentation (material properties), Raman spectroscopy (chemical), and small-angle X-ray scattering (mineral crystallization and structure).ResultsThe cranial and caudal sites of tibiae are structurally and biochemically different within control bones. In response to loading, cranial and caudal sites increase in cortical thickness with reduced mineralization (−14 and −3%, p < 0.01, respectively) and crystallinity (−1.4 and −0.3%, p < 0.05, respectively). Along the length of the loaded bones, collagen content becomes more heterogeneous on the caudal site and the mineral/collagen increases distally at both sites.ConclusionBone structure and composition are heterogeneous, finely tuned, adaptive, and site-specifically responsive at the micro-scale to maintain optimal function. Manipulation of this heterogeneity may affect bone strength, relative to specific applied loads.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-016-3846-6) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 58%

Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The aim of this study was to understand if an in vitro loading set up of tenocytes leads to similar regulations of cell morphology and gene expression, as in axial compressive loading of the mouse tibia and Achilles tendon. We used comparable loading parameters in both models, and the in vivo model used in this study is a well-established model to investigate the bone formation in response of mechanical loading [24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes—A Pilot Study

Fleischhacker

Klatte‐Schulz

Minkwitz

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Mechanical force is a key factor for the maintenance, adaptation, and function of tendons. Investigating the impact of mechanical loading in tenocytes and tendons might provide important information on in vivo tendon mechanobiology. Therefore, the study aimed at understanding if an in vitro loading set up of tenocytes leads to similar regulations of cell shape and gene expression, as loading of the Achilles tendon in an in vivo mouse model. In vivo: The left tibiae of mice (n = 12) were subject to axial cyclic compressive loading for 3 weeks, and the Achilles tendons were harvested. The right tibiae served as the internal non-loaded control. In vitro: tenocytes were isolated from mice Achilles tendons and were loaded for 4 h or 5 days (n = 6 per group) based on the in vivo protocol. Histology showed significant differences in the cell shape between in vivo and in vitro loading. On the molecular level, quantitative real-time PCR revealed significant differences in the gene expression of collagen type I and III and of the matrix metalloproteinases (MMP). Tendon-associated markers showed a similar expression profile. This study showed that the gene expression of tendon markers was similar, whereas significant changes in the expression of extracellular matrix (ECM) related genes were detected between in vivo and in vitro loading. This first pilot study is important for understanding to which extent in vitro stimulation set-ups of tenocytes can mimic in vivo characteristics.

show abstract

“…Changes in multiple cellular processes might contribute to the altered bone‐healing response with age. Reductions in the number of stem cells, migration, proliferation or differentiation capacity, altered revascularization, as well as altered tissue material properties have all been associated with a reduced regenerative capacity with increasing age. However, which of these components mainly contribute to the alterations observed at the tissue level remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Age-Related Changes in the Mechanical Regulation of Bone Healing Are Explained by Altered Cellular Mechanoresponse

Borgiani

Figge²,

Kruck³

et al. 2019

Journal of Bone and Mineral Research

Self Cite

View full text Add to dashboard Cite

Increasing age is associated with a reduced bone regeneration potential and increased risk of morbidities and mortality. A reduced bone formation response to mechanical loading has been shown with aging, and it remains unknown if the interplay between aging and mechanical stimuli during regeneration is similar to adaptation. We used a combined in vivo/in silico approach to investigate age-related alterations in the mechanical regulation of bone healing and identified the relative impact of altered cellular function on tissue patterns during the regenerative cascade. To modulate the mechanical environment, femoral osteotomies in adult and elderly mice were stabilized using either a rigid or a semirigid external fixator, and the course of healing was evaluated using histomorphometric and micro-CT analyses at 7, 14, and 21 days post-surgery. Computer models were developed to investigate the influence of the local mechanical environment within the callus on tissue formation patterns. The models aimed to identify the key processes at the cellular level that alter the mechanical regulation of healing with aging. Fifteen age-related biological alterations were investigated on two levels (adult and elderly) with a design of experiments setup. We show a reduced response to changes in fixation stability with age, which could be explained by reduced cellular mechanoresponse, simulated as alteration of the ranges of mechanical stimuli driving mesenchymal stem cell differentiation. Cellular mechanoresponse has been so far widely ignored as a therapeutic target in aged patients. Our data hint to mechanotherapeutics as a potential treatment to enhance bone healing in the elderly. Fig. 1. Finite element models of the mice femoral osteotomy stabilized with a rigid (A) and a semirigid fixator (B) and predicted compressive principal strain distributions within the callus. Callus regions under investigation and their dimensions are reported. Ps = periosteal; I = intracortical; Es = endosteal. [Color figure can be viewed at wileyonlinelibrary.com] Journal of Bone and Mineral Research AGE-RELATED ALTERED CELLULAR MECHANORESPONSE IN BONE HEALING 1925 ■ 30. Willie BM, Birkhold AI, Razi H, et al. Diminished response to in vivo mechanical loading in trabecular and not cortical bone in ◼ 14 BORGIANI ET AL.

show abstract

Skeletal maturation substantially affects elastic tissue properties in the endosteal and periosteal regions of loaded mice tibiae

Cited by 10 publications

References 71 publications

Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone

Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone

In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes—A Pilot Study

Age-Related Changes in the Mechanical Regulation of Bone Healing Are Explained by Altered Cellular Mechanoresponse

Contact Info

Product

Resources

About