Tenascin-C expression and its associated pathway in BMSCs following co-culture with mechanically stretched ligament fibroblasts

Zhao, Bing; Hu, Mengcai; Wu, Hongyan; Ren, Chen; Wang, Jianshe; Cui, Shihong

doi:10.3892/mmr.2017.6329

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…In addition, cells in the TGFβ3 group exhibited a unique but consistent tenascin C immunofluorescent signature characterized by a high intensity fluorescence encircling the nucleus and moderate intensity fluorescence adjacent to the cell membrane, first noted on Day 4 of culture. Similar patterns and relative intensity of TenC immunofluorescence have been documented in other tenogenic differentiation or tenocyte characterization trials [ 70 , 71 ], and in an experiment assessing the effect of a BMSC coculture with mechanically stretched ligament fibroblasts, a hyperintense TenC immunofluorescent signature was directly correlated with TenC mRNA expression, quantified using a reverse-transcription-quantitative polymerase chain reaction (RT-qPCR) [ 72 ]. Therefore, based on superior tendon-associated glycoprotein expression upregulation and appropriate morphologic, behavioral, and proliferative changes, we can conclude that TGFβ3 alone was the most effective tenogenic factor in this experiment, and we can confirm that the rAdMSC lineage can be effectively directed toward a tenogenic lineage in vitro, thus, confirming its tenogenic potential.…”

Section: Discussionmentioning

confidence: 57%

Mesenchymal Stem Cell Use in Acute Tendon Injury: In Vitro Tenogenic Potential vs. In Vivo Dose Response

et al. 2022

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Stem cell therapy for the treatment of tendon injury is an emerging clinical practice in the fields of human and veterinary sports medicine; however, the therapeutic benefit of intralesional transplantation of mesenchymal stem cells in tendonitis cases is not well designed. Questions persist regarding the overall tenogenic potential and efficacy of this treatment alone. In this study, we aimed to isolate a rat mesenchymal stem cell lineage for in vitro and in vivo use, to assess the effects of growth factor exposure in vitro on cell morphology, behavior, and tendon-associated glycoprotein production, and to assess the therapeutic potential of intralesional stem cells, as a function of dose, in vivo. First, rat adipose-derived (rAdMSC) and bone marrow-derived (rBMSC) stem cell lineages were isolated, characterized with flow cytometric analysis, and compared in terms of proliferation (MTS assay) and cellular viability (calcein AM staining). Rat AdMSCs displayed superior proliferation and more homogenous CD 73, CD 44H, and CD 90 expression as compared to rBMSC. Next, the tenogenic differentiation potential of the rAdMSC lineage was tested in vitro through isolated and combined stimulation with reported tenogenic growth factors, transforming growth factor (TGF)-β3 and connective tissue growth factor (CTGF). We found that the most effective tenogenic factor in terms of cellular morphologic change, cell alignment/orientation, sustained cellular viability, and tendon-associated glycoprotein upregulation was TGFβ3, and we confirmed that rAdMSC could be induced toward a tenogenic lineage in vitro. Finally, the therapeutic potential of rAdMSCs as a function of dose was assessed using a rat acute Achilles tendon injury model. Amounts of 5 × 105 (low dose) and 4 × 106 (high dose) were used. Subjectively, on the gross morphology, the rAdMSC-treated tendons exhibited fewer adhesions and less scar tissue than the control tendons; however, regardless of the rAdMSC dose, no significant differences in histological grade or tissue collagen I deposition were noted between the rAdMSC-treated and control tendons. Collectively, rAdMSCs exhibited appropriate stem cell markers and tenogenic potential in vitro, but the clinical efficacy of intralesional implantation of undifferentiated cells in acute tendonitis cases could not be proven. Further investigation into complementary therapeutics or specialized culture conditions prior to implantation are warranted.

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Section: Discussionmentioning

confidence: 57%

Mesenchymal Stem Cell Use in Acute Tendon Injury: In Vitro Tenogenic Potential vs. In Vivo Dose Response

et al. 2022

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“…TNC promotes neurite outgrowth from cortical neurons grown on a monolayer of astrocytes . Stimulation via mechanical stretch may promote the synthesis of TNC and bone marrow stromal cell (BMSC) differentiation into pelvic ligament fibroblasts . LGALS1 plays a role in regulating apoptosis, cell proliferation, and cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Proteomics of Uterosacral Ligament Connective Tissue from Women with and without Pelvic Organ Prolapse

Pan

Chen

et al. 2018

Proteomics Clinical Apps

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Purpose: Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study is to identify differentially expressed proteins (DEPs) in the uterosacral ligaments of women with and without pelvic organ prolapse (POP) and analyze their relationships to cellular mechanisms involved in the pathogenesis of POP. Experimental design: Uterosacral ligament connective tissue from four patients with POP and four control women undergo iTRAQ analysis followed by ingenuity pathway analysis (IPA) of DEPs. DEPs are validated using Western blot analysis. Results: A total of 1789 unique protein sequences are identified in the uterosacral ligament connective tissues. The expression levels of 88 proteins are significantly different between prolapse and control groups (ࣙ1.2-fold, p < 0.05). IPA demonstrates the association of 14 DEPs with "Connective Tissue Function." Among them, fibromodulin, collagen alpha-1 (XIV) chain, calponin-1, tenascin, and galectin-1 appear most likely to play a role in the etiology of POP. Conclusions and clinical relevance: At least six proteins not previously associated with the pathogenesis of POP with biologic functions that suggest a plausible relationship to the disorder are identified. These results may be helpful for furthering the understanding of the pathophysiological mechanisms of POP.

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“…Tenascin presence in pelvic floor relaxation is closely linked to alteration of extracellular proteins of supporting tissues [17]. Bone marrow mesenchymal cells have the potential to differentiate into a variety of cells, including osteoblasts, chondroblasts and adipose cells.…”

Section: A B C Total All Groups A-(b+c) A-c A-b B-cmentioning

confidence: 99%

Immunohistochemical expression of tenascin and elastin in women with pelvic organ prolapse and/or without stress urinary incontinence

Liapis¹,

Bakas²,

Agatha³

et al. 2021

Clin Obstet Gynecol Reprod Med

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Background and aim: Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) constitute entities of pelvic floor disorders and most often occur simultaneously in the same patient, adversely affecting women's quality of life. The pathogenesis of pelvic organ prolapse and stress urinary incontinence is not fully understood. The pelvic viscera are maintained in their place thanks to interconnection of levator ani muscles, cardinal and uterosacral ligaments, and pubocervical and rectovaginal fascia. Ligaments and fascia consist mainly of connective tissue. Alterations in the metabolism of its extracellular matrix could contribute POP and SUI. The aim of this study was to assess the metabolism of extracellular matrix components in relation to the immunohistochemical expression of tenascin and elastin in patients with POP and/or without SUI.Methods: In the present study, we included 90 adult Greek women; 30 women with POP and SUI, 30 women with POP and no SUI, and 30 controls. For the immunohistochemical study, 90 biopsies were obtained after hysterectomy from the vagina (pubocervical fascia) and the attachment areas of uterosacral and cardinal ligaments. The specimens were studied for immunohistochemical evaluation of tenascin and elastin. Results:Tenascin was strongly expressed in all samples obtained from women with prolapse. Patients with total prolapse showed enhanced immunoactivity to the tenascin-specific antigen near connective tissue and around the wall of vessels. Continent patients with only POP and the control group were more likely to have weakly positive or negative tenascin immunoreaction in stromal cells and local expression in muscles/vessels. Regarding the immunohistochemical response of elastin expression, we observed an increased number of patients with reduced elastin and decreased number of patients with positive expression of elastin in patients with prolapse and SUI.Conclusions: These alterations on the metabolism of extracellular matrix components of the connective tissue seem to contribute to the pathogenesis of POP and SUI and may aid in non-surgical treatment of these disorders.

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Tenascin-C expression and its associated pathway in BMSCs following co-culture with mechanically stretched ligament fibroblasts

Cited by 6 publications

References 41 publications

Mesenchymal Stem Cell Use in Acute Tendon Injury: In Vitro Tenogenic Potential vs. In Vivo Dose Response

Mesenchymal Stem Cell Use in Acute Tendon Injury: In Vitro Tenogenic Potential vs. In Vivo Dose Response

Proteomics of Uterosacral Ligament Connective Tissue from Women with and without Pelvic Organ Prolapse

Immunohistochemical expression of tenascin and elastin in women with pelvic organ prolapse and/or without stress urinary incontinence

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