Osteopontin and skeletal muscle myoblasts: Association with muscle regeneration and regulation of myoblast function in vitro

Uaesoontrachoon, Kitipong; Yoo, H.-J.; Tudor, Elizabeth; Pike, Robert N.; Mackie, Eleanor J.; Pagel, Charles N.

doi:10.1016/j.biocel.2008.03.020

Cited by 104 publications

(107 citation statements)

References 47 publications

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“…Substratum OPN promotes myoblast attachment in murine cells (Uaesoontrachoon et al . 2008). Conversely, soluble OPN‐a inhibits myotube fusion.…”

Section: Discussionmentioning

confidence: 99%

“…Expression of OPN is rapidly induced in acute and chronic muscle injury, with expression primarily localized to infiltrating immune cells and proliferating myogenic cells (Uaesoontrachoon et al . 2008; Zanotti et al . 2011; Paliwal et al .…”

Section: Introductionmentioning

confidence: 99%

“…In myogenic cells, OPN expression is upregulated with inflammatory stimuli and degeneration/remodelling (Uaesoontrachoon et al . 2008; Paliwal et al . 2012).…”

Section: Introductionmentioning

confidence: 99%

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OPN‐a induces muscle inflammation by increasing recruitment and activation of pro‐inflammatory macrophages

Many

Yokosaki

Uaesoontrachoon

et al. 2016

Experimental Physiology

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New Findings What is the central question of this study? What is the functional relevance of OPN isoform expression in muscle pathology? What is the main finding and its importance? The full‐length human OPN‐a isoform is the most pro‐inflammatory isoform in the muscle microenvironment, acting on macrophages and myoblasts in an RGD‐integrin‐dependent manner. OPN‐a upregulates expression of tenascin‐C (TNC), a known Toll‐like receptor 4 (TLR4) agonist. Blocking TLR4 signalling inhibits the pro‐inflammatory effects of OPN‐a, suggesting that a potential mechanism of OPN action is by promoting TNC–TLR4 signalling. Although osteopontin (OPN) is an important mediator of muscle remodelling in health and disease, functional differences in human spliced OPN variants in the muscle microenvironment have not been characterized. We thus sought to define the pro‐inflammatory activities of human OPN isoforms (OPN‐a, OPN‐b and OPN‐c) on cells present in regenerating muscle. OPN transcripts were quantified in normal and dystrophic human and dog muscle. Human macrophages and myoblasts were stimulated with recombinant human OPN protein isoforms, and cytokine mRNA and protein induction was assayed. OPN isoforms were greatly increased in dystrophic human (OPN‐a > OPN‐b > OPN‐c) and dog muscle (OPN‐a = OPN‐c). In healthy human muscle, mechanical loading also upregulated OPN‐a expression (eightfold; P < 0.01), but did not significantly upregulate OPN‐c expression (twofold; P > 0.05). In vitro, OPN‐a displayed the most pronounced pro‐inflammatory activity among isoforms, acting on both macrophages and myoblasts. In vitro and in vivo data revealed that OPN‐a upregulated tenascin‐C (TNC), a known Toll‐like receptor 4 (TLR4) agonist. Inhibition of TLR4 signalling attenuated OPN‐mediated macrophage cytokine production. In summary, OPN‐a is the most abundant and functionally active human spliced isoform in the skeletal muscle microenvironment. Here, OPN‐a promotes pro‐inflammatory signalling in both macrophages and myoblasts, possibly through induction of TNC–TLR4 signalling. Together, our findings suggest that specific targeting of OPN‐a and/or TNC signalling in the damaged muscle microenvironment may be of therapeutic relevance.

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“…Substratum OPN promotes myoblast attachment in murine cells (Uaesoontrachoon et al . 2008). Conversely, soluble OPN‐a inhibits myotube fusion.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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OPN‐a induces muscle inflammation by increasing recruitment and activation of pro‐inflammatory macrophages

Many

Yokosaki

Uaesoontrachoon

et al. 2016

Experimental Physiology

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“…11,12 OPN has been found to be expressed in various cell types in addition to osteocytes. 13,14 This secretory protein was reported to be involved in the metastasis of cancer cells and the inflammation of rheumatoid arthritis through the Arginine-Glycine-Aspartic Acid (RGD) sequence located adjacent to the cleavage site of matrix metalloproteinases. 15,16 OPN levels have been reported to be increased in atherosclerotic lesions.…”

Section: Introductionmentioning

confidence: 99%

Aldosterone-induced osteopontin gene transcription in vascular smooth muscle cells involves glucocorticoid response element

et al. 2011

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Osteopontin (OPN) is known to be one of the cytokines that is involved in the vascular inflammation caused by aldosterone (Aldo). Previous reports have shown that Aldo increases OPN transcripts, and the mechanisms for this remain to be clarified. In this study, we investigated how Aldo increases OPN transcripts in the vascular smooth muscle cells of rats. Aldosterone increased OPN transcripts time-dependently as well as dose-dependently. This increase was diminished by eplerenone, a mineralocorticoid receptor (MR) antagonist. Luciferase promoter assays showed that the OPN promoter deleted to the À1599 site retained the same promoting ability as the full-length OPN promoter when stimulated by 10 À7 M Aldo, but the promoter deleted to the À1300 site lost the promoting ability. A glucocorticoid response element (GRE) is located in that deleted region. Luciferase assays of a mutated promoter without the GRE lost the luciferase upregulation, although mutated promoters with the deletion of other consensus sites maintained the promoter activity. The binding of the Aldo-MR complex to the GRE fragment was confirmed by an electrophoretic-mobility shift assay. This is the first report showing that Aldo regulates the transcriptional levels of OPN and inflammatory responses in the vasculature through a specific GRE site in the OPN promoter region.

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“…Uaesoontrachoon et al, reported that myoblast cultures with fibroblast growth factor-2, transforming growth factor-β1, interleukin 1-beta or thrombin showed significantly increased OPN expression [24]. These results suggested that myoblasts are an important source of OPN in damaged muscle.…”

Section: Methodsmentioning

confidence: 97%

Expression of Osteopontin in Oral Squamous Cell Carcinoma and its Surgical Margins-An Immunohistochemical Study

Subramani

Narasimhan

Thiyagarajan

et al. 2015

JCDR

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Osteopontin and skeletal muscle myoblasts: Association with muscle regeneration and regulation of myoblast function in vitro

Cited by 104 publications

References 47 publications

OPN‐a induces muscle inflammation by increasing recruitment and activation of pro‐inflammatory macrophages

OPN‐a induces muscle inflammation by increasing recruitment and activation of pro‐inflammatory macrophages

Aldosterone-induced osteopontin gene transcription in vascular smooth muscle cells involves glucocorticoid response element

Expression of Osteopontin in Oral Squamous Cell Carcinoma and its Surgical Margins-An Immunohistochemical Study

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