Weight loading young chicks inhibits bone elongation and promotes growth plate ossification and vascularization

2005 ◽  
Vol 98 (6) ◽  
pp. 2381-2389 ◽  
Author(s):  
A. Reich ◽  
N. Jaffe ◽  
A. Tong ◽  
I. Lavelin ◽  
O. Genina ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Growth Plate ◽  
Developmental Process ◽  
Mechanical Strain ◽  
Cell Counting ◽  
Mechanical Stimuli ◽  
Growth Plates ◽  
Average Width ◽  
The Matrix ◽  
Weight Loading

The mechanical stimuli resulting from weight loading play an important role in mature bone remodeling. However, the effect of weight loading on the developmental process in young bones is less well understood. In this work, chicks were loaded with bags weighing 10% of their body weight during their rapid growth phase. The increased load reduced the length and diameter of the long bones. The average width of the bag-loaded group's growth plates was 75 ± 4% that of the controls, and the plates showed increased mineralization. Northern blot analysis, in situ hybridization, and longitudinal cell counting of mechanically loaded growth plates showed narrowed expression zones of collagen types II and X compared with controls, with no differences between the relative proportions of those areas. An increase in osteopontin (OPN) expression with loading was most pronounced at the bone-cartilage interface. This extended expression overlapped with tartarate-resistant acid phosphatase staining and with the front of the mineralized matrix in the chondro-osseous junction. Moreover, weight loading enhanced the penetration of blood vessels into the growth plates and enhanced the gene expression of the matrix metalloproteinases MMP9 and MMP13 in those growth plates. On the basis of these results, we speculate that the mechanical strain on the chondrocytes in the growth plate causes overexpression of OPN, MMP9, and MMP13. The MMPs enable penetration of the blood vessels, which carry osteoclasts and osteoblasts. OPN recruits the osteoclasts to the cartilage-bone border, thus accelerating cartilage resorption in this zone and subsequent ossification which, in turn, contributes to the observed phenotype of narrower growth plate and shorter bones.

Epi- and metaphyseal morphology in the long bones of BDIX/Han rats

1996 ◽  
Vol 30 (1) ◽  
pp. 35-41 ◽  
Author(s):  
C. Stark ◽  
B. Kahrmann ◽  
E. Walzel
Keyword(s):  
Growth Plate ◽  
Long Bones ◽  
Adult Rats ◽  
Growth Plates ◽  
The Matrix ◽  
Different Strains ◽  
Regressive Changes

Development and morphology of the epiphyses of the long bones were investigated in 93 adult rats of 7 different strains (BDIX/Han, BDE/Han, BN/Han, DA/Han, LEW/Han, AVN/IpcV/Wistar/Rehbrücke, Shoe: WIST) from the age of 14 weeks up to the age of 78 weeks. Strain-related differences were found in the development of the secondary centre of ossification, which was retarded in the BDIX/Han rats. Furthermore, closure of the growth plate started earlier in the BDIX/Han rats. In addition various regressive changes were detected in the growth plates of long bones of all rats, but not of the ribs. The frequency and extent of these changes varied between individuals and strains. Degeneration of the matrix and necrosis were already observed at 14 weeks of age.

The molecular mechanism of mechanotransduction in vascular homeostasis and disease

2020 ◽  
Vol 134 (17) ◽  
pp. 2399-2418
Author(s):  
Yoshito Yamashiro ◽  
Hiromi Yanagisawa
Keyword(s):  
Shear Stress ◽  
Blood Vessels ◽  
Vessel Wall ◽  
Vascular Diseases ◽  
Cell Interactions ◽  
Aortic Aneurysms ◽  
Cyclic Stretch ◽  
Mechanical Stimuli ◽  
Vascular Homeostasis ◽  
Matrix Cell

Abstract Blood vessels are constantly exposed to mechanical stimuli such as shear stress due to flow and pulsatile stretch. The extracellular matrix maintains the structural integrity of the vessel wall and coordinates with a dynamic mechanical environment to provide cues to initiate intracellular signaling pathway(s), thereby changing cellular behaviors and functions. However, the precise role of matrix–cell interactions involved in mechanotransduction during vascular homeostasis and disease development remains to be fully determined. In this review, we introduce hemodynamics forces in blood vessels and the initial sensors of mechanical stimuli, including cell–cell junctional molecules, G-protein-coupled receptors (GPCRs), multiple ion channels, and a variety of small GTPases. We then highlight the molecular mechanotransduction events in the vessel wall triggered by laminar shear stress (LSS) and disturbed shear stress (DSS) on vascular endothelial cells (ECs), and cyclic stretch in ECs and vascular smooth muscle cells (SMCs)—both of which activate several key transcription factors. Finally, we provide a recent overview of matrix–cell interactions and mechanotransduction centered on fibronectin in ECs and thrombospondin-1 in SMCs. The results of this review suggest that abnormal mechanical cues or altered responses to mechanical stimuli in EC and SMCs serve as the molecular basis of vascular diseases such as atherosclerosis, hypertension and aortic aneurysms. Collecting evidence and advancing knowledge on the mechanotransduction in the vessel wall can lead to a new direction of therapeutic interventions for vascular diseases.

scholarly journals Initial mechanical conditions within an optimized bone scaffold do not ensure bone regeneration – an in silico analysis

2021 ◽  
Author(s):  
Camille Perier-Metz ◽  
Georg N. Duda ◽  
Sara Checa
Keyword(s):  
Bone Regeneration ◽  
In Silico ◽  
Volume Fraction ◽  
Computer Modelling ◽  
Mechanical Strain ◽  
In Silico Analysis ◽  
Bone Volume ◽  
Mechanical Stimuli ◽  
Design Strategies ◽  
Scaffold Design

AbstractLarge bone defects remain a clinical challenge because they do not heal spontaneously. 3-D printed scaffolds are a promising treatment option for such critical defects. Recent scaffold design strategies have made use of computer modelling techniques to optimize scaffold design. In particular, scaffold geometries have been optimized to avoid mechanical failure and recently also to provide a distinct mechanical stimulation to cells within the scaffold pores. This way, mechanical strain levels are optimized to favour the bone tissue formation. However, bone regeneration is a highly dynamic process where the mechanical conditions immediately after surgery might not ensure optimal regeneration throughout healing. Here, we investigated in silico whether scaffolds presenting optimal mechanical conditions for bone regeneration immediately after surgery also present an optimal design for the full regeneration process. A computer framework, combining an automatic parametric scaffold design generation with a mechano-biological bone regeneration model, was developed to predict the level of regenerated bone volume for a large range of scaffold designs and to compare it with the scaffold pore volume fraction under favourable mechanical stimuli immediately after surgery. We found that many scaffold designs could be considered as highly beneficial for bone healing immediately after surgery; however, most of them did not show optimal bone formation in later regenerative phases. This study allowed to gain a more thorough understanding of the effect of scaffold geometry changes on bone regeneration and how to maximize regenerated bone volume in the long term.

scholarly journals Mechanical plasticity of collagen directs branch elongation in human mammary gland organoids

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
B. Buchmann ◽  
L. K. Engelbrecht ◽  
P. Fernandez ◽  
F. P. Hutterer ◽  
M. K. Raich ◽  
...  
Keyword(s):  
Mechanical Response ◽  
Developmental Process ◽  
Branching Morphogenesis ◽  
Collagen Network ◽  
Mechanical Tension ◽  
Structural Reorganization ◽  
Linear Response Regime ◽  
Human Mammary Gland ◽  
The Matrix ◽  
Tension Generation

AbstractEpithelial branch elongation is a central developmental process during branching morphogenesis in diverse organs. This fundamental growth process into large arborized epithelial networks is accompanied by structural reorganization of the surrounding extracellular matrix (ECM), well beyond its mechanical linear response regime. Here, we report that epithelial ductal elongation within human mammary organoid branches relies on the non-linear and plastic mechanical response of the surrounding collagen. Specifically, we demonstrate that collective back-and-forth motion of cells within the branches generates tension that is strong enough to induce a plastic reorganization of the surrounding collagen network which results in the formation of mechanically stable collagen cages. Such matrix encasing in turn directs further tension generation, branch outgrowth and plastic deformation of the matrix. The identified mechanical tension equilibrium sets a framework to understand how mechanical cues can direct ductal branch elongation.

scholarly journals Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review

Micromachines ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 765
Author(s):  
Qianbin Zhao ◽  
Tim Cole ◽  
Yuxin Zhang ◽  
Shi-Yang Tang
Keyword(s):  
Cell Culture ◽  
Shear Stress ◽  
Cultured Cells ◽  
Mechanical Strain ◽  
3D Cell Culture ◽  
Small Scale ◽  
Mechanical Stimuli ◽  
Human Organ ◽  
Organ On A Chip

Organ-on-a-chip (OOC) uses the microfluidic 3D cell culture principle to reproduce organ- or tissue-level functionality at a small scale instead of replicating the entire human organ. This provides an alternative to animal models for drug development and environmental toxicology screening. In addition to the biomimetic 3D microarchitecture and cell–cell interactions, it has been demonstrated that mechanical stimuli such as shear stress and mechanical strain significantly influence cell behavior and their response to pharmaceuticals. Microfluidics is capable of precisely manipulating the fluid of a microenvironment within a 3D cell culture platform. As a result, many OOC prototypes leverage microfluidic technology to reproduce the mechanically dynamic microenvironment on-chip and achieve enhanced in vitro functional organ models. Unlike shear stress that can be readily generated and precisely controlled using commercial pumping systems, dynamic systems for generating proper levels of mechanical strains are more complicated, and often require miniaturization and specialized designs. As such, this review proposes to summarize innovative microfluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.

scholarly journals Cam morphology in young male football players mostly develops before proximal femoral growth plate closure: a prospective study with 5-yearfollow-up

2018 ◽  
Vol 53 (9) ◽  
pp. 532-538 ◽  
Author(s):  
Pim van Klij ◽  
Marinus P Heijboer ◽  
Abida Z Ginai ◽  
Jan A N Verhaar ◽  
Jan H Waarsing ◽  
...  
Keyword(s):  
Growth Plate ◽  
Alpha Angle ◽  
Football Players ◽  
Growth Plates ◽  
Time Points ◽  
Open Growth Plate ◽  
Morphology Development ◽  
Open Growth ◽  
Cam Morphology

ObjectivesCam morphology is not completely understood. The aim of this study was threefold: (1) to investigate if cam morphology development is associated with growth plate status; (2) to examine whether cam morphology continues to develop after growth plate closure; and (3) to qualitatively describe cam morphology development over 5-year follow-up.MethodsAcademy male football players (n=49) participated in this prospective 5-year follow-up study (baseline 12–19 years old). Anteroposterior and frog-leg lateral views were obtained at baseline (142 hips), 2.5-year (126 hips) and 5-year follow-up (98 hips). Cam morphology on these time points was defined as: (A) visual scores of the anterior head-neck junction, classified as: (1) normal, (2) flattening, and (3) prominence; and (B) alpha angle ≥60°. Proximal femoral growth plates were classified as open or closed. Cam morphology development was defined as every increase in visual score and/or increase in alpha angle from <60° to ≥60°, between two time points. This resulted in 224 measurements for cam morphology development analysis.ResultsCam morphology development was significantly associated with open growth plates based on visual score (OR: 10.03, 95% CI 3.49 to 28.84, p<0.001) and alpha angle (OR: 2.85, 95% CI 1.18 to 6.88, p=0.020). With both definitions combined, cam developed in 104 of 142 hips during follow-up. Of these 104 hips, cam developed in 86 hips (82.7%) with open growth plate and in 18 hips (17.3%) with a closed growth plate. Cam morphology developed from 12 to 13 years of age until growth plate closure around 18 years.ConclusionCam morphology of the hip is more likely to develop with an open growth plate.

scholarly journals Progressive recruitment of distal MEC-4 channels determines touch response strength in C. elegans

2019 ◽  
Author(s):  
S. Katta ◽  
A. Sanzeni ◽  
A. Das ◽  
M. Vergassola ◽  
M.B. Goodman
Keyword(s):  
Temporal Dynamics ◽  
Mechanical Strain ◽  
Tissue Mechanics ◽  
Mechanical Stimuli ◽  
Patch Clamp Recording ◽  
Open Probability ◽  
C Elegans ◽  
Somatosensory Neurons ◽  
Touch Response

AbstractTouch deforms, or strains, the skin beyond the immediate point of contact. The spatiotemporal nature of the touch-induced strain fields depend on the mechanical properties of the skin and the tissues below. Somatosensory neurons that sense touch branch out within the skin and rely on a set of mechano-electrical transduction channels distributed within their dendrites to detect mechanical stimuli. Here, we sought to understand how tissue mechanics shape touch-induced mechanical strain across the skin over time and how individual channels located in different regions of the strain field contribute to the overall touch response. We leveraged C. elegans’ touch receptor neurons (TRNs) as a simple model amenable to in vivo whole-cell patch clamp recording and an integrated experimental-computational approach to dissect the mechanisms underlying the spatial and temporal dynamics that we observed. Consistent with the idea that strain is produced at a distance, we show that delivering strong stimuli outside the anatomical extent of the neuron is sufficient to evoke MRCs. The amplitude and kinetics of the MRCs depended on both stimulus displacement and speed. Finally, we found that the main factor responsible for touch sensitivity is the recruitment of progressively more distant channels by stronger stimuli, rather than modulation of channel open probability. This principle may generalize to somatosensory neurons with more complex morphologies.SummaryThrough experiment and simulation, Katta et al. reveal that pushing faster and deeper recruits more and more distant mechano-electrical transduction channels during touch. The net result is a dynamic receptive field whose size and shape depends on tissue mechanics, stimulus parameters, and channel distribution within sensory neurons.

scholarly journals Cyclic Mechanical Strain Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through GCN5 and Wnt/β-Catenin

2021 ◽  
Vol 9 ◽  
Author(s):  
Yanchang Liu ◽  
Wendan Cheng ◽  
Yao Zhao ◽  
Liang Gao ◽  
Yongyun Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Mechanical Stress ◽  
Critical Role ◽  
Mechanical Strain ◽  
Biological Behavior ◽  
Mechanical Stimuli ◽  
Mechanical Signals ◽  
Alkaline Phosphatase Staining

Bone marrow mesenchymal stem cells (BMSCs) play a critical role in bone formation and are extremely sensitive to external mechanical stimuli. Mechanical signals can regulate the biological behavior of cells on the surface of titanium-related prostheses and inducing osteogenic differentiation of BMSCs, which provides the integration of host bone and prosthesis benefits. But the mechanism is still unclear. In this study, BMSCs planted on the surface of TiO2 nanotubes were subjected to cyclic mechanical stress, and the related mechanisms were explored. The results of alkaline phosphatase staining, real-time PCR, and Western blot showed that cyclic mechanical stress can regulate the expression level of osteogenic differentiation markers in BMSCs on the surface of TiO2 nanotubes through Wnt/β-catenin. As an important member of the histone acetyltransferase family, GCN5 exerted regulatory effects on receiving mechanical signals. The results of the ChIP assay indicated that GCN5 could activate the Wnt promoter region. Hence, we concluded that the osteogenic differentiation ability of BMSCs on the surface of TiO2 nanotubes was enhanced under the stimulation of cyclic mechanical stress, and GCN5 mediated this process through Wnt/β-catenin.

scholarly journals Ultrastructural localization of the C-propeptide released from type II procollagen in fetal bovine growth plate cartilage.

1996 ◽  
Vol 44 (5) ◽  
pp. 433-443 ◽  
Author(s):  
E R Lee ◽  
C E Smith ◽  
R Poole
Keyword(s):  
Growth Plate ◽  
Ultrastructural Localization ◽  
Collagen Fibrils ◽  
Type Ii ◽  
Guanidinium Hydrochloride ◽  
High Affinity ◽  
Sds Page ◽  
The Matrix ◽  
Fetal Bovine ◽  
Mineralized Matrix

We used immunochemical and immunoelectron gold techniques to determine whether the C-propeptide previously identified in the matrix of endochondral cartilage (CPII) was still a part of the Type 11 procollagen molecule or had been released from it. Guanidinium hydrochloride extraction, followed by SDS-PAGE and Western blotting techniques and immunoelectron localization, revealed that predominantly only the released form (hereafter referred to as released CPII) was detected. The ultrastructural distribution of this CPII was examined with affinity-purified antibodies and with immunogold or immunoperoxidase localization techniques in the presence or absence of embedding resins. These methods yielded similar results. Although no significant amount of this CPII was retained in the matrix after guanidinium hydrochloride extraction, it was present in two recognizable sites under normal conditions, i.e., locally concentrated in a random association with collagen fibrils in the nonmineralized matrix and mainly concentrated in interfibrillar mineralizing sites in the mineralized matrix. These results suggest that the C-propeptide that has been released from Type II procollagen associates with collagen fibrils and then preferentially associates with mineralizing sites when these form in the endochondral cartilage. The significance of this preference for mineral is not known but may have something to do with its high affinity for hydroxyapatite.

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