Stromal cell-derived factor-1 (CXCL12) and its role in bone and muscle biology

Gilbert, W. Barritt; Bragg, Robert; Elmansi, Ahmed M.; McGee‐Lawrence, Meghan E.; Isales, Carlos M.; Hamrick, Mark W.; Hill, William; Fulzele, Sadanand

doi:10.1016/j.cyto.2019.154783

Cited by 41 publications

(42 citation statements)

References 127 publications

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“…Stromal cell-derived factor-1 (SDF-1), also known as CXCL12, is a member of the homeostatic CXC family of chemokines, with emerging roles in bones, joints, and muscles [9]. However, the role of SDF-1 in the pathogenesis of OA has yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

Exogenous Stromal Cell-Derived Factor-1 (SDF-1) Suppresses the NLRP3 Inflammasome and Inhibits Pyroptosis in Synoviocytes from Osteoarthritic Joints via Activation of the AMPK Signaling Pathway

Wang

Mobasheri

Zhang

et al. 2021

Preprint

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ObjectiveNLRP3 inflammasome may play a key role in OA pathogenesis. Stromal cell-derived factor-1 (SDF-1) is a homeostatic CXC chemokine. Since the role of SDF-1 in OA has not been explored, this study aimed to examine the effect of SDF-1 on NLRP3 inflammasome and pyroptosis in synoviocytes from OA joints.Materials and MethodsHuman synovium was obtained from OA patients for isolation of primary synoviocytes and a murine model of collagen-induced OA was established for testing intra-articular injections of SDF-1. Immunoblotting assays were used to examine the effects and underlying mechanism of action of SDF-1 on NLRP3 inflammasome and synoviocyte pyroptosis in synoviocytes. Inhibitors of AMPK and PI3K-mTOR were utilized to investigate the key signaling pathways involved in SDF-1-mediated OA inflammasome formation and pyroptosis.ResultsSynoviocytes from OA joints exhibited significantly higher expression of NLRP3 inflammasome and biomarkers of synoviocyte pyroptosis relative to healthy individuals. This was confirmed in the collagen-induced OA model, where OA synoviocytes had a significantly lower SDF-1 expression than healthy ones. SDF-1 treatment in synoviocytes of OA patients and collagen-induced OA led to significant downregulation in the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers. Inhibition of the AMPK signaling pathway significantly suppressed the inhibitory effect of SDF-1 on NLRP3 inflammasome expression of OA synoviocytes. However, blocking the SDF-1-activated PI3K-mTOR signaling pathway could still suppress the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers.ConclusionsSDF-1 ameliorates NLRP3 inflammasome and pyroptosis in OA synoviocytes through activation of the AMPK signaling pathway. Therefore, SDF-1 may be a novel therapeutic target for OA.

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Section: Introductionmentioning

confidence: 99%

Exogenous Stromal Cell-Derived Factor-1 (SDF-1) Suppresses the NLRP3 Inflammasome and Inhibits Pyroptosis in Synoviocytes from Osteoarthritic Joints via Activation of the AMPK Signaling Pathway

Wang

Mobasheri

Zhang

et al. 2021

Preprint

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“…Another nding showed the periostin is expressed in the cardiac broblasts, which can result in cardiomyocyte maturation and innervation 18 . G-protein-coupled receptors (GPCRs), Regulators of G protein signaling (RGS), and their downstream pathways are involved in various physiological and pathological processes [19][20][21] including in ammation, metabolism, cancer, and pain [22][23][24][25][26][27][28] . As a signi cant heterotrimeric G protein, GNAI2 ameliorates cell proliferation and inhibits apoptosis processes 26 .…”

Section: Discussionmentioning

confidence: 99%

Identification of driver genes and biological signaling for alcoholic myopathy

Li¹,

Wang²,

Gu³

2021

Preprint

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Long-term alcohol consumption contributes to muscle weakness and atrophy. However, the mechanism and biological functions are still not clear. In this study, we aim to identify the significantly changed genes and potential signaling pathways in the gastrocnemius and plantaris muscle from C57BL/6Hsd mice by analyzing RNA sequence. The GSE183665 dataset was created by using the Illumina NovaSeq 6000 (Mus musculus). The KEGG and GO analyses showed that "cell migration", "cell adhesion", and "apoptosis" are major biological processes in the skeletal muscles. Moreover, we identified a number of genes including POSTN, GNAI2, MMP2, ELN, CCND1, CXCL12, COL6A1, COL6A2, SFRP2, and FSTL1 by using the PPI network and Reactome map. Thus, our study may shed light on the development of drugs on alcohol myopathy.

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“…Sox9, CXCR4, and CXCL12 expressing cells were also observed within the cartilage of developing nasal septum, suggesting their involvement in chondrogenesis. Several in vitro and in vivo studies on the role of CXCL12-CXCR4 signaling in relation to bone formation have been performed ( Gilbert et al, 2019 ). CXCL12 expression in non-differentiated mesenchymal stem cells in bone was demonstrated, but toward the end of osteogenic differentiation CXCL12 was downregulated ( Ito, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

CXCL12-CXCR4 Interplay Facilitates Palatal Osteogenesis in Mice

Verheijen

Suttorp

Rheden

et al. 2020

Front. Cell Dev. Biol.

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Cranial neural crest cells (CNCCs), identified by expression of transcription factor Sox9, migrate to the first branchial arch and undergo proliferation and differentiation to form the cartilage and bone structures of the orofacial region, including the palatal bone. Sox9 promotes osteogenic differentiation and stimulates CXCL12-CXCR4 chemokinereceptor signaling, which elevates alkaline phosphatase (ALP)-activity in osteoblasts to initiate bone mineralization. Disintegration of the midline epithelial seam (MES) is crucial for palatal fusion. Since we earlier demonstrated chemokine-receptor mediated signaling by the MES, we hypothesized that chemokine CXCL12 is expressed by the disintegrating MES to promote the formation of an osteogenic center by CXCR4-positive osteoblasts. Disturbed migration of CNCCs by excess oxidative and inflammatory stress is associated with increased risk of cleft lip and palate (CLP). The cytoprotective heme oxygenase (HO) enzymes are powerful guardians harnessing injurious oxidative and inflammatory stressors and enhances osteogenic ALP-activity. By contrast, abrogation of HO-1 or HO-2 expression promotes pregnancy pathologies. We postulate that Sox9, CXCR4, and HO-1 are expressed in the ALP-activity positive osteogenic regions within the CNCCs-derived palatal mesenchyme. To investigate these hypotheses, we studied expression of Sox9, CXCL12, CXCR4, and HO-1 in relation to palatal osteogenesis between E15 and E16 using (immuno)histochemical staining of coronal palatal sections in wild-type (wt) mice. In addition, the effects of abrogated HO-2 expression in HO-2 KO mice and inhibited HO-1 and HO-2 activity by administrating HO-enzyme activity inhibitor SnMP at E11 in wt mice were investigated at E15 or E16 following palatal fusion. Overexpression of Sox9, CXCL12, CXCR4, and HO-1 was detected in the ALP-activity positive osteogenic regions within the palatal mesenchyme. Overexpression of Sox9 and CXCL12 by the disintegrating MES was detected. Neither palatal fusion nor MES disintegration seemed affected by either HO-2 abrogation or inhibition of HO-activity. Sox9 progenitors seem important to maintain the CXCR4-positive osteoblast pool to drive osteogenesis. Sox9 expression may facilitate MES disintegration and palatal fusion by promoting epithelial-to-mesenchymal transformation (EMT). CXCL12 expression by

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Stromal cell-derived factor-1 (CXCL12) and its role in bone and muscle biology

Cited by 41 publications

References 127 publications

Exogenous Stromal Cell-Derived Factor-1 (SDF-1) Suppresses the NLRP3 Inflammasome and Inhibits Pyroptosis in Synoviocytes from Osteoarthritic Joints via Activation of the AMPK Signaling Pathway

Exogenous Stromal Cell-Derived Factor-1 (SDF-1) Suppresses the NLRP3 Inflammasome and Inhibits Pyroptosis in Synoviocytes from Osteoarthritic Joints via Activation of the AMPK Signaling Pathway

Identification of driver genes and biological signaling for alcoholic myopathy

CXCL12-CXCR4 Interplay Facilitates Palatal Osteogenesis in Mice

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