Impaired Alignment of Bone Matrix Microstructure Associated with Disorganized Osteoblast Arrangement in Malignant Melanoma Metastasis

Matsugaki, Aira; Kimura, Yumi; Watanabe, Ryota; Nakamura, Fumihito; Takehana, Ryo; Nakano, Takayoshi

doi:10.3390/biom11020131

Cited by 7 publications

(8 citation statements)

References 33 publications

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“…The results showed that the apatite orientation of femurs loaded with uniaxial forces was significantly higher than that of the unloaded femurs. We previously reported that the arrangement of the collagen/apatite microstructure was determined by controlling the artificial loading to the bone [17,34,35]. The findings of the present study are consistent with the changes in apatite orientation observed in these in vivo studies.…”

Section: Discussionsupporting

confidence: 92%

“…An Ex Vivo Bone Culture Model E16.5 mice (ICR; Japan SLC, Shizuoka, Japan) were anesthetized, and femurs were removed under a light microscope. Referring to previously reported ex vivo bone culture models [34,35], embryonic femurs were cultured in 96-well plates (IWAKI, Tokyo, Japan) and commercially pure (CP) titanium specimens (weights: 0.5 or 1.0 g) for 7 days at 37 • C in 5% CO 2 . The bone was fractured by a 1.5 g load.…”

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confidence: 99%

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A Novel Ex Vivo Bone Culture Model for Regulation of Collagen/Apatite Preferential Orientation by Mechanical Loading

Watanabe

Matsugaki

Ishimoto

et al. 2022

IJMS

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The anisotropic microstructure of bone, composed of collagen fibers and biological apatite crystallites, is an important determinant of its mechanical properties. Recent studies have revealed that the preferential orientation of collagen/apatite composites is closely related to the direction and magnitude of in vivo principal stress. However, the mechanism of alteration in the collagen/apatite microstructure to adapt to the mechanical environment remains unclear. In this study, we established a novel ex vivo bone culture system using embryonic mouse femurs, which enabled artificial control of the mechanical environment. The mineralized femur length significantly increased following cultivation; uniaxial mechanical loading promoted chondrocyte hypertrophy in the growth plates of embryonic mouse femurs. Compressive mechanical loading using the ex vivo bone culture system induced a higher anisotropic microstructure than that observed in the unloaded femur. Osteocytes in the anisotropic bone microstructure were elongated and aligned along the long axis of the femur, which corresponded to the principal loading direction. The ex vivo uniaxial mechanical loading successfully induced the formation of an oriented collagen/apatite microstructure via osteocyte mechano-sensation in a manner quite similar to the in vivo environment.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

A Novel Ex Vivo Bone Culture Model for Regulation of Collagen/Apatite Preferential Orientation by Mechanical Loading

Watanabe

Matsugaki

Ishimoto

et al. 2022

IJMS

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“…Changes in bone's ECM composition and organization are characteristic for bone pathologies like osteoporosis, osteogenesis imperfecta, and bone metastasis (Bala and Seeman, 2015;Bishop, 2016;Karunaratne et al, 2016;Matsugaki et al, 2021). Therefore, in vitro models that aim at studying changes in bone ECM under the influence of treatments would benefit from improved control over organic matrix formation and subsequent mineralization (Hadida and Marchat, 2020;de Wildt et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Tissue engineering strategies are nowadays increasingly applied for the creation of in vitro models of healthy or pathological bone, aiming at improving preclinical treatment development while addressing the principle of reduction, refinement, and replacement of animal experiments (3Rs) (Balls et al, 1995; Caddeo et al, 2017; Holmes et al, 2009; Owen and Reilly, 2018). Changes in bone’s ECM composition and organization are characteristic for bone pathologies like osteoporosis, osteogenesis imperfecta, and bone metastasis (Bala and Seeman, 2015; Bishop, 2016; Karunaratne et al, 2016; Matsugaki et al, 2021). Therefore, in vitro models that aim at studying changes in bone ECM under the influence of treatments would benefit from improved control over organic matrix formation and subsequent mineralization (Hadida and Marchat, 2020; de Wildt et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Characterization of three-dimensional bone-like tissue growth and organization under influence of curvature and directional fluid flow

Wildt

Zhao

Lauwers

et al. 2022

Preprint

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The transition in the field of bone tissue engineering from bone regeneration to three-dimensional in vitro models has come with the challenge of recreating a dense and anisotropic bone-like extracellular matrix with cell culture. The creation of such an organized bone-like extracellular matrix has received little attention thus far. Although the mechanism by which bone extracellular matrix gains its structure is not fully understood, curvature (especially concavities), mechanical loading due to deformations or directional fluid flow, and osteocyte signaling have been identified as potential contributors. Here, guided by computational simulations, we evaluated three-dimensional cell and bone-like tissue growth and organization in a concave channel with and without directional fluid flow stimulation. Human bone-marrow derived mesenchymal stromal cells were seeded on donut-shaped silk fibroin scaffolds and stimulated to undergo osteogenic differentiation for 42 days statically or in a flow perfusion bioreactor. Constructs were investigated for cell distribution, and tissue growth and organization on day 14, 28, and 42. As a result, directional fluid flow was able to improve bone-like tissue growth but not organization. After 28 days of culture, when osteogenic differentiation was likely accomplished, cells tended to have a small preference for orientation in the tangential (i.e., circumferential) direction of the channel. Based on our results, we suggest that three-dimensional bone-like tissue anisotropy might be guided by curvature, while extracellular matrix production can be increased through the application of fluid shear stress. With this study, an initial attempt in three-dimensions was made to improve the resemblance of in vitro produced bone-like extracellular matrix to the physiological bone extracellular matrix.

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“…Studies have revealed that these inflammatory cytokines function by promoting RANKL production, reducing OPG production, and/or up-regulating RANK on osteoclast precursors, indirectly affecting osteoclastogenesis [ 4 , 10 , 11 ]. Meanwhile, these inflammatory cytokines inhibit osteoblast proliferation [ 12 , 13 ] and disrupt unidirectional osteoblast alignment [ 14 , 15 ], resulting in improper bone regeneration. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid.…”

Section: Introductionmentioning

confidence: 99%

Targeting S1PRs as a Therapeutic Strategy for Inflammatory Bone Loss Diseases—Beyond Regulating S1P Signaling

2021

IJMS

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As G protein coupled receptors, sphingosine-1-phosphate receptors (S1PRs) have recently gained attention for their role in modulating inflammatory bone loss diseases. Notably, in murine studies inhibiting S1PR2 by its specific inhibitor, JTE013, alleviated osteoporosis induced by RANKL and attenuated periodontal alveolar bone loss induced by oral bacterial inflammation. Treatment with a multiple S1PRs modulator, FTY720, also suppressed ovariectomy-induced osteoporosis, collagen or adjuvant-induced arthritis, and apical periodontitis in mice. However, most previous studies and reviews have focused mainly on how S1PRs manipulate S1P signaling pathways, subsequently affecting various diseases. In this review, we summarize the underlying mechanisms associated with JTE013 and FTY720 in modulating inflammatory cytokine release, cell chemotaxis, and osteoclastogenesis, subsequently influencing inflammatory bone loss diseases. Studies from our group and from other labs indicate that S1PRs not only control S1P signaling, they also regulate signaling pathways induced by other stimuli, including bacteria, lipopolysaccharide (LPS), bile acid, receptor activator of nuclear factor κB ligand (RANKL), IL-6, and vitamin D. JTE013 and FTY720 alleviate inflammatory bone loss by decreasing the production of inflammatory cytokines and chemokines, reducing chemotaxis of inflammatory cells from blood circulation to bone and soft tissues, and suppressing RANKL-induced osteoclast formation.

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Impaired Alignment of Bone Matrix Microstructure Associated with Disorganized Osteoblast Arrangement in Malignant Melanoma Metastasis

Cited by 7 publications

References 33 publications

A Novel Ex Vivo Bone Culture Model for Regulation of Collagen/Apatite Preferential Orientation by Mechanical Loading

A Novel Ex Vivo Bone Culture Model for Regulation of Collagen/Apatite Preferential Orientation by Mechanical Loading

Characterization of three-dimensional bone-like tissue growth and organization under influence of curvature and directional fluid flow

Targeting S1PRs as a Therapeutic Strategy for Inflammatory Bone Loss Diseases—Beyond Regulating S1P Signaling

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