IU Indianapolis ScholarWorks :: Browsing by Subject "Mechanical loading"

Browsing by Subject "Mechanical loading"

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Cell and matrix response of temporomandibular cartilage to mechanical loading
(Elsevier, 2016-02) Utreja, Achint; Dyment, Nathaniel A.; Yadav, Sumit; Villa, Max M.; Li, Yingcui; Jiang, Xi; Nanda, Ravindra; Rowe, David W.; Department of Orthodontics and Oral Facial Genetics, School of Dentistry
OBJECTIVES: The generation of transgenic mice expressing green fluorescent proteins (GFPs) has greatly aided our understanding of the development of connective tissues such as bone and cartilage. Perturbation of a biological system such as the temporomandibular joint (TMJ) within its adaptive remodeling capacity is particularly useful in analyzing cellular lineage progression. The objectives of this study were to determine: (i) if GFP reporters expressed in the TMJ indicate the different stages of cell maturation in fibrocartilage and (ii) how mechanical loading affects cellular response in different regions of the cartilage. DESIGN/METHODS: Four-week-old transgenic mice harboring combinations of fluorescent reporters (Dkk3-eGFP, Col1a1(3.6 kb)-GFPcyan, Col1a1(3.6 kb)-GFPtpz, Col2a1-GFPcyan, and Col10a1-RFPcherry) were used to analyze the expression pattern of transgenes in the mandibular condylar cartilage (MCC). To study the effect of TMJ loading, animals were subjected to forced mouth opening with custom springs exerting 50 g force for 1 h/day for 5 days. Dynamic mineralization and cellular proliferation (EdU-labeling) were assessed in loaded vs control mice. RESULTS: Dkk3 expression was seen in the superficial zone of the MCC, followed by Col1 in the cartilage zone, Col2 in the prehypertrophic zone, and Col10 in the hypertrophic zone at and below the tidemark. TMJ loading increased expression of the GFP reporters and EdU-labeling of cells in the cartilage, resulting in a thickness increase of all layers of the cartilage. In addition, mineral apposition increased resulting in Col10 expression by unmineralized cells above the tidemark. CONCLUSION: The TMJ responded to static loading by forming thicker cartilage through adaptive remodeling.
Control of Bone Matrix Properties by Osteocytes
(Frontiers Media, 2021-01-18) Creecy, Amy; Damrath, John G.; Wallace, Joseph M.; Biomedical Engineering, School of Engineering and Technology
Osteocytes make up 90–95% of the cellular content of bone and form a rich dendritic network with a vastly greater surface area than either osteoblasts or osteoclasts. Osteocytes are well positioned to play a role in bone homeostasis by interacting directly with the matrix; however, the ability for these cells to modify bone matrix remains incompletely understood. With techniques for examining the nano- and microstructure of bone matrix components including hydroxyapatite and type I collagen becoming more widespread, there is great potential to uncover novel roles for the osteocyte in maintaining bone quality. In this review, we begin with an overview of osteocyte biology and the lacunar–canalicular system. Next, we describe recent findings from in vitro models of osteocytes, focusing on the transitions in cellular phenotype as they mature. Finally, we describe historical and current research on matrix alteration by osteocytes in vivo, focusing on the exciting potential for osteocytes to directly form, degrade, and modify the mineral and collagen in their surrounding matrix.
The Interaction of Biological Factors with Mechanical Signals in Bone Adaptation: Recent Developments
(Current Science Inc., 2012-06) Robling, Alexander G.; Department of Anatomy & Cell Biology, IU School of Medicine
Mechanotransduction in bone is fundamental to proper skeletal development. Deficiencies in signaling mechanisms that transduce physical forces to effector cells can have severe consequences for skeletal integrity. Therefore, a solid understanding of the cellular and molecular components of mechanotransduction is crucial for correcting skeletal modeling and remodeling errors and designing effective therapies. In recent years, progress has been made on many fronts regarding our understanding of bone cell mechanotransduction, including subcellular localization of mechanosensitive components in bone cells, the discovery of mechanosensitive G-protein- coupled receptors, identification of new ion channels and larger pores (eg, hemichannels) involved in physical signal transduction, and cell adhesion proteins, among others. These and other recent mechanisms are reviewed to provide a synthesis of recent experimental findings, in the larger context of whole bone adaptation.
Load-dependent collagen fiber architecture data of representative bovine tendon and mitral valve anterior leaflet tissues as quantified by an integrated opto-mechanical system
(Elsevier, 2020-02) Jett, Samuel V.; Hudson, Luke T.; Baumwart, Ryan; Bohnstedt, Bradley N.; Mir, Arshid; Burkhart, Harold M.; Holzapfel, Gerhard A.; Wu, Yi; Lee, Chung-Hao; Neurological Surgery, School of Medicine
The data presented in this article provide load-dependent collagen fiber architecture (CFA) of one representative bovine tendon tissue sample and two representative porcine mitral valve anterior leaflet tissues, and they are stored in a MATLAB MAT-file format. Each dataset contains: (i) the number of pixel points, (ii) the array of pixel's x- and y-coordinates, (iii) the three acquired pixel intensity arrays, and (iv) the Delaunay triangulation for visualization purpose. This dataset is associated with a companion journal article, which can be consulted for further information about the methodology, results, and discussion of the opto-mechanical characterization of the tissue's CFA's (Jett etal. [1]).
Mechanical loading attenuates breast cancer-associated bone metastasis in obese mice by regulating the bone marrow microenvironment
(Wiley, 2021) Huang, Menglu; Liu, Hong; Zhu, Lei; Li, Xinle; Li, Jie; Yang, Shuang; Liu, Daquan; Song, Xiaomeng; Yokota, Hiroki; Zhang, Ping; Biomedical Engineering, School of Engineering and Technology
Breast cancer, a common malignancy for women, preferentially metastasizes to bone and obesity elevates the chance of its progression. While mechanical loading can suppress obesity and tumor-driven osteolysis, its effect on bone-metastasized obese mice has not been investigated. Here, we hypothesized that mechanical loading can lessen obesity-associated bone degradation in tumor-invaded bone by regulating the fate of bone marrow-derived cells. In this study, the effects of mechanical loading in obese mice were evaluated through X-ray imaging, histology, cytology, and molecular analyses. Tumor inoculation to the tibia elevated body fat composition, osteolytic lesions, and tibia destruction, and these pathologic changes were stimulated by the high-fat diet (HFD). However, mechanical loading markedly reduced these changes. It suppressed osteoclastogenesis by downregulating receptor activator of nuclear factor Kappa-B ligand and cathepsin K and promoted osteogenesis, which was associated with the upregulation of OPG and downregulation of C/enhancer-binding protein alpha and proliferator-activated receptor gamma for adipogenic differentiation. Furthermore, it decreased the levels of tumorigenic genes such as Rac1, MMP9, and interleukin 1β. In summary, this study demonstrates that although a HFD aggravates bone metastases associated with breast cancer, mechanical loading significantly protected tumor-invaded bone by regulating the fate of bone marrow-derived cells. The current study suggests that mechanical loading can provide a noninvasive, palliative option for alleviating breast cancer-associated bone metastasis, in particular for obese patients.
Mechanical Loading Mitigates Osteoarthritis Symptoms by Regulating the Inflammatory Microenvironment
(SSRN, 2021-06-14) Zhang, Weiwei; Li, Xinle; Li, Jie; Wang, Xiaoyu; Liu, Daquan; Zhai, Lidong; Ding, Beibei; Li, Guang; Sun, Yuting; Yokota, Hiroki; Zhang, Ping; Biomedical Engineering, Purdue School of Engineering and Technology
Osteoarthritis (OA) is one of the most common chronic diseases, in which inflammatory responses in the articular cavity induce chondrocyte apoptosis and cartilage degeneration. While mechanical loading is reported to mitigate synovial inflammation, the mechanism and pathways for the loading-driven improvement of OA symptoms remain unclear. In this research, we evaluated the loading effects on the M1/M2 polarization of synovial macrophages via performing molecular, cytology, and histology analyses. In the OA groups, the cell layer of the synovial lining was enlarged with an increase in cell density. Also, M1 macrophages were polarized and pro-inflammatory cytokines were increased. In contrast, in the OA group with mechanical loading cartilage degradation was reduced and synovial inflammation was alleviated. Notably, the polarization of M1 macrophages was diminished by mechanical loading, while that of M2 macrophages was increased. Furthermore, mechanical loading decreased the levels of pro-inflammatory cytokines such as IL-1β and TNF-α and suppressed PI3K/AKT/NF-κB signaling. Consistently, NF-κB inhibited decreased the polarization of M1 macrophages in RAW264.7 macrophages. Taken together, this study demonstrates that mechanical loading changes the ratio of M1 and M2 macrophage polarization via regulating PI3K/AKT/NF-κB signaling and provides chondroprotective effects in the mouse OA model.
Mechanical Regulation of Bone Homeostasis Through p130Cas-mediated Alleviation of NF-κB Activity
(American Association for the Advancement of Science, 2019-09) Miyazaki, T.; Zhao, Z.; Ichihara, Y.; Yoshino, D.; Imamura, T.; Sawada, K.; Hayano, S.; Kamioka, H.; Mori, S.; Hirata, H.; Araki, K.; Kawauchi, K.; Shigemoto, K.; Tanaka, S.; Bonewald, L. F.; Honda, H.; Shinohara, M.; Nagao, M.; Ogata, T.; Harada, I.; Sawada, Y.; Medicine, School of Medicine
Mechanical loading plays an important role in bone homeostasis. However, molecular mechanisms behind the mechanical regulation of bone homeostasis are poorly understood. We previously reported p130Cas (Cas) as a key molecule in cellular mechanosensing at focal adhesions. Here, we demonstrate that Cas is distributed in the nucleus and supports mechanical loading-mediated bone homeostasis by alleviating NF-κB activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-κB activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-κB-mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-κB activity. Collectively, fluid shear stress-dependent Cas-mediated alleviation of NF-κB activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-κB together with systemic distribution of interstitial fluid, the Cas-NF-κB interplay may also underpin regulatory mechanisms in other tissues and organs.
Muscle secreted factors enhance activation of the PI3K/Akt and β-catenin pathways in murine osteocytes
(Elsevier, 2023) Lara-Castillo, N.; Masunaga, J.; Brotto, L.; Vallejo, J. A.; Javid, K.; Wacker, M. J.; Brotto, M.; Bonewald, L. F.; Johnson, M. L.; Medicine, School of Medicine
Skeletal muscle and bone interact at the level of mechanical loading through the application of force by muscles to the skeleton and more recently focus has been placed on molecular/biochemical coupling of these two tissues. We sought to determine if muscle and muscle-derived factors were essential to the osteocyte response to loading. Botox® induced muscle paralysis was used to investigate the role of muscle contraction during in vivo tibia compression loading. 5-6 month-old female TOPGAL mice had their right hindlimb muscles surrounding the tibia injected with either BOTOX® or saline. At four days post injections when muscle paralysis peaked, the right tibia was subjected to a single session of in vivo compression loading at ∼2600 με. At 24 h post-load we observed a 2.5-fold increase in β-catenin signaling in osteocytes in the tibias of the saline injected mice, whereas loading of tibias from Botox® injected mice failed to active β-catenin signaling in osteocytes. This suggests that active muscle contraction produces a factor(s) that is necessary for or conditions the osteocyte's ability to respond to load. To further investigate the role of muscle derived factors, MLO-Y4 osteocyte-like cells and a luciferase based β-catenin reporter (TOPflash-MLO-Y4) cell line we developed were treated with conditioned media (CM) from C2C12 myoblasts (MB) and myotubes (MT) and ex vivo contracted Extensor Digitorum Longus (EDL) and Soleus (Sol) muscles under static or loading conditions using fluid flow shear stress (FFSS). 10 % C2C12 myotube CM, but not myoblast or NIH3T3 fibroblast cells CM, induced a rapid activation of the Akt signaling pathway, peaking at 15 min and returning to baseline by 1-2 h under static conditions. FFSS applied to MLO-Y4 cells for 2 h in the presence of 10 % MT-CM resulted in a 6-8 fold increase in pAkt compared to a 3-4 fold increase under control or when exposed to 10 % MB-CM. A similar response was observed in the presence of 10 % EDL-CM, but not in the presence of 10 % Sol-CM. TOPflash-MLO-Y4 cells were treated with 10 ng/ml Wnt3a in the presence or absence of MT-CM. While MT-CM resulted in a 2-fold activation and Wnt3a produced a 10-fold activation, the combination of MT-CM + Wnt3a resulted in a 25-fold activation of β-catenin signaling, implying a synergistic effect of factors in MT-CM with Wnt3a. These data provide clear evidence that specific muscles and myotubes produce factors that alter important signaling pathways involved in the response of osteocytes to mechanical load. These data strongly suggest that beyond mechanical loading there is a molecular coupling of muscle and bone.
Progressive skeletal benefits of physical activity when young as assessed at the midshaft humerus in male baseball players
(SpringerLink, 2017-07) Warden, Stuart J.; Weatherholt, Alyssa M.; Gudeman, Andrew S.; Mitchell, Drew C.; Thompson, William R.; Fuchs, Robyn K.; Physical Therapy, School of Health and Human Sciences
Physical activity benefits the skeleton, but there is contrasting evidence regarding whether benefits differ at different stages of growth. The current study demonstrates that physical activity should be encouraged at the earliest age possible and be continued into early adulthood to gain most skeletal benefits. INTRODUCTION: The current study explored physical activity-induced bone adaptation at different stages of somatic maturity by comparing side-to-side differences in midshaft humerus properties between male throwing athletes and controls. Throwers present an internally controlled model, while inclusion of control subjects removes normal arm dominance influences. METHODS: Throwing athletes (n = 90) and controls (n = 51) were categorized into maturity groups (pre, peri, post-early, post-mid, and post-late) based on estimated years from peak height velocity (<-2, -2 to 2, 2 to 4, 4 to 10, and >10 years). Side-to-side percent differences in midshaft humerus cortical volumetric bone mineral density (Ct.vBMD) and bone mineral content (Ct.BMC); total (Tt.Ar), medullary (Me.Ar), and cortical (Ct.Ar) areas; average cortical thickness (Ct.Th); and polar Strength Strain Index (SSIP) were assessed. RESULTS: Significant interactions between physical activity and maturity on side-to-side differences in Ct.BMC, Tt.Ar, Ct.Ar, Me.Ar, Ct.Th, and SSIP resulted from the following: (1) greater throwing-to-nonthrowing arm differences than dominant-to-nondominant arm differences in controls (all p < 0.05) and (2) throwing-to-nonthrowing arm differences in throwers being progressively greater across maturity groups (all p < 0.05). Regional analyses revealed greatest adaptation in medial and lateral sectors, particularly in the three post-maturity groups. Years throwing predicted 59% of the variance of the variance in throwing-to-nonthrowing arm difference in SSIP (p < 0.001). CONCLUSION: These data suggest that physical activity has skeletal benefits beginning prior to and continuing beyond somatic maturation and that a longer duration of exposure to physical activity has cumulative skeletal benefits. Thus, physical activity should be encouraged at the earliest age possible and be continued into early adulthood to optimize skeletal benefits.
Skeletal Functions of Voltage Sensitive Calcium Channels
(Springer, 2021) Wright, Christian S.; Robling, Alexander G.; Farach-Carson, Mary C.; Thompson, William R.; Physical Therapy, School of Health and Human Sciences
Voltage-sensitive calcium channels (VSCCs) are ubiquitous multimeric protein complexes that are necessary for the regulation of numerous physiological processes. VSCCs regulate calcium influx and various intracellular processes including muscle contraction, neurotransmission, hormone secretion, and gene transcription, with function specificity defined by the channel‟s subunits and tissue location. The functions of VSCCs in bone are often overlooked since bone is not considered an electrically excitable tissue. However, skeletal homeostasis and adaptation relies heavily on VSCCs. Inhibition or deletion of VSCCs decreases osteogenesis, impairs skeletal structure, and impedes anabolic responses to mechanical loading. While the functions of VSCCs in osteoclasts is less clear, VSCCs have distinct but complementary functions in osteoblasts and osteocytes. This review details the structure, function, and nomenclature of VSCCs, followed by a comprehensive description of the known functions of VSCCs in bone cells and their regulation of bone development, bone formation, and mechanotransduction.

Browsing by Subject "Mechanical loading"

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