Aberrant structure of fibrillar collagen and elevated levels of advanced glycation end products typify delayed fracture healing in the diet-induced obesity mouse model

Khajuria, Deepak Kumar; Soliman, Mostafa M.; Elfar, John C.; Lewis, Gregory S.; Abraham, Thomas; Kamal, Fadia; Elbarbary, Reyad A.

doi:10.1016/j.bone.2020.115436

Cited by 22 publications

(41 citation statements)

References 63 publications

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“…This interesting phenomenon has attracted the attention of this research group. Reading previous research literature found that there have been reports verifying abnormal osteogenic differentiation or poor fracture healing caused by obesity 22,23 . In this study, we also verified this phenomenon through in vivo and in vitro experiments.…”

Section: Discussionsupporting

confidence: 80%

“…Reading previous research literature found that there have been reports verifying abnormal osteogenic differentiation or poor fracture healing caused by obesity. 22,23 In this study, we also verified this phenomenon through in vivo and in vitro experiments. Exosomes have been proven to affect cell functions as an important link in cell-to-cell communication.…”

Section: Discussionsupporting

confidence: 66%

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Obesity regulates miR‐467/HoxA10 axis on osteogenic differentiation and fracture healing by BMSC‐derived exosome LncRNA H19

Wang

Chen

Zhao

et al. 2021

J Cellular Molecular Medi

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This study explored the therapeutic effect of bone marrow mesenchymal stem cell‐derived exosomes on the treatment of obesity‐induced fracture healing. Quantitative real‐time PCR was used to detect the expression of lncRNA H19, miR‐467 and Hoxa10 and combined with WB detection to detect osteogenic markers (RUNX2, OPN, OCN). Determine whether exosomes have entered BMSCs by immunofluorescence staining. Alkaline phosphatase (ALP) and alizarin red staining (ARS) staining were used to detect ALP activity and calcium deposition. We found that high‐fat treatment can inhibit the secretion of BMSCs‐derived exosomes and affect the expression of H19 carried by them. In vivo and in vitro experiments show that high‐fat or obesity factors can inhibit the expression of osteogenic markers and reduce the staining activity of ALP and ARS. The treatment of exosomes from normal sources can reverse the phenomenon of osteogenic differentiation and abnormal fracture healing. Further bioinformatics analysis found that miR‐467 as a regulatory molecule of lncRNA H19 and Hoxa10, and we verified the targeting relationship of the three through dual luciferase report experiments. Further, we found similar phenomena in ALP and ARS staining. Bone marrow mesenchymal stem cell‐derived exosomes improve fracture healing caused by obesity.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 66%

Obesity regulates miR‐467/HoxA10 axis on osteogenic differentiation and fracture healing by BMSC‐derived exosome LncRNA H19

Wang

Chen

Zhao

et al. 2021

J Cellular Molecular Medi

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“…An altered hierarchical structure of collagen molecules affects the mineralization process that occurs within and around fibers. 8,9,31 Herein, bone-like nodules were characterized at different scales using single scan polarization-resolved second harmonic generation (SS-pSHG) and polarized light (PLM) microscopies. The nonlinear signal being sensitive to the polarization state of the excitation light, SS-pSHG emission is likely to depend on the optical anisotropy that results from the collagen molecular organization.…”

Section: Resultsmentioning

confidence: 99%

“…The nature and organization of the collagenous fibrillar network are critical for bone physiology, 7 where sparse and disorganized fibrils result in inadequate bone mineralization. 8,9 Although considerable breakthroughs have been achieved over the past 30 years, resulting in a wealth of knowledge in many fields (i.e. biochemistry, cell biology, and molecular biology), the systematic characterization of bone-like nodules at the submicrometric scale is barely described in the literature.…”

Section: Introductionmentioning

confidence: 99%

Mechanobiologically induced bone-like nodules: Matrix characterization from micro to nanoscale

Rammal

Dubus

Bercu

et al. 2020

Nanomedicine: Nanotechnology, Biology and Medicine

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In bone tissue engineering, stem cells are known to form inhomogeneous bone-like nodules on a micrometric scale. Herein, micro-and nano-infrared (IR) micro-spectroscopies were used to decipher the chemical composition of the bone-like nodule. Histological and immunohistochemical analyses revealed a cohesive tissue with bone-markers positive cells surrounded by dense mineralized type-I collagen. Micro-IR gathered complementary information indicating a nonmature collagen at the top and periphery and a mature collagen within the nodule. Atomic force microscopy combined to IR (AFM-IR) analyses showed distinct spectra of "cell" and "collagen" rich areas. In contrast to the "cell" area, spectra of "collagen" area revealed the presence of carbohydrate moieties of collagen and/or the presence of glycoproteins. However, it was not possible to determine the collagen maturity, due to strong bands overlapping and/or possible protein orientation effects. Such findings could help developing protocols to allow a reliable characterization of in vitro generated complex bone tissues.

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“…Type I collagen typically produces a strong FSHG signal, while Type II collagen typically produces a strong BSHG signal. While other fibrillar collagens (Col III, V, XI, XXIV, XXVII) are present in the joint tissues, they generate weak SHG signals 14 , 15 . FSHG and BSHG signals can then be analyzed to determine fiber content, width, and orientation.…”

Section: Introductionmentioning

confidence: 99%

Structural changes in the collagen network of joint tissues in late stages of murine OA

Yoshioka

Young

Khajuria

et al. 2022

Sci Rep

Self Cite

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Osteoarthritis (OA) is the most prevalent degenerative joint disease, resulting in joint pain, impaired movement, and structural changes. As the ability of joint tissue to resist stress is mainly imparted by fibrillar collagens in the extracellular matrix, changes in the composition and structure of collagen fibers contribute to the pathological remodeling observed in OA joints that includes cartilage degeneration, subchondral bone (SCB) sclerosis, and meniscal damage. Using the established OA model of destabilization of the medial meniscus (DMM) in C57BL/6J mice, we performed a comprehensive analysis of the content and structure of collagen fibers in the articular cartilage, subchondral bone, and menisci using complementary techniques, which included second harmonic generation microscopy and immunofluorescence staining. We found that regions exposed to increased mechanical stress in OA mice, typically closest to the site of injury, had increased collagen fiber thickness, dysregulated fiber formation, and tissue specific changes in collagen I and II (Col I and Col II) expression. In cartilage, OA was associated with decreased Col II expression in all regions, and increased Col I expression in the anterior and posterior regions. Col I fiber thickness was increased in all regions with disorganization in the center region. In the superficial SCB, all regions exhibited increased Col I expression and fiber thickness in OA mice; no changes were detected in the deeper regions of the subchondral bone except for increased Col I fiber thickness. In the menisci, OA led to increased Col I and Col II expression in the vascular and avascular regions of the anterior meniscus with increased Col I fiber thickness in these regions. Similar changes were observed only in the vascular region of the posterior meniscus. Our findings provide, for the first time, comprehensive insights into the microarchitectural changes of extracellular matrix in OA and serve as guidelines for studies investigating therapies that target collagenous changes as means to impede the progression of osteoarthritis.

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Aberrant structure of fibrillar collagen and elevated levels of advanced glycation end products typify delayed fracture healing in the diet-induced obesity mouse model

Cited by 22 publications

References 63 publications

Obesity regulates miR‐467/HoxA10 axis on osteogenic differentiation and fracture healing by BMSC‐derived exosome LncRNA H19

Obesity regulates miR‐467/HoxA10 axis on osteogenic differentiation and fracture healing by BMSC‐derived exosome LncRNA H19

Mechanobiologically induced bone-like nodules: Matrix characterization from micro to nanoscale

Structural changes in the collagen network of joint tissues in late stages of murine OA

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