ArticleTissue engineering and regenerative medicine2022
The Neuropeptide Spexin Promotes the Osteoblast Differentiation of MC3T3-E1 Cells via the MEK/ERK Pathway and Bone Regeneration in a Mouse Calvarial Defect Model.
Article in Tissue engineering and regenerative medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Spexin-induced MC3T3-E1 cell-derived exosomes enhance osteoblast differentiation.Journal of bone and mineral metabolism · 2025Article
- Purified bone xenografts: A novel and efficient animal bone substitute derived from an optimized supercritical COMaterials today. Bio · 2025Article
- The guanine nucleotide exchange factor DOCK5 negatively regulates osteoblast differentiation and BMP2-induced bone regeneration via the MKK3/6 and p38 signaling pathways.Experimental & molecular medicine · 2025Article
- The transcription factor BBX regulates phosphate homeostasis through the modulation of FGF23.Experimental & molecular medicine · 2024Article
- Activation of Nuclear Factor Erythroid 2-Related Factor 2 Transcriptionally Upregulates Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Expression and Inhibits Ectopic Calcification in Mice.Antioxidants (Basel, Switzerland) · 2024Article
- Efficient preparation of high-purity and intact mesenchymal stem cell-derived extracellular vesicles.Analytical and bioanalytical chemistry · 2024Article
- Spexin role in human granulosa cells physiology and PCOS: expression and negative impact on steroidogenesis and proliferation†.Biology of reproduction · 2023Article
- Effects of Red LED Irradiation in Enhancing the Mineralization of Human Dental Pulp Cells In Vitro.International journal of molecular sciences · 2023Article
- Osteogenesis Performance of Boronized Ti6Al4V/HA Composites Prepared by Microwave Sintering: In Vitro and In Vivo Studies.Materials (Basel, Switzerland) · 2022Article
- Bu-Gu-Sheng-Sui decoction promotes osteogenesisFrontiers in pharmacology · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe neural regulation of bone regeneration has emerged recently. Spexin (SPX) is a novel neuropeptide and regulates multiple biological functions. However, the effects of SPX on osteogenic differentiation need to be further investigated. Therefore, the aim of this study is to investigate the effects of SPX on osteogenic differentiation, possible underlying mechanisms, and bone regeneration.
methodsIn this study, MC3T3-E1 cells were treated with various concentrations of SPX. Cell proliferation, osteogenic differentiation marker expressions, alkaline phosphatase (ALP) activity, and mineralization were evaluated using the CCK-8 assay, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), ALP staining, and alizarin red S staining, respectively. To determine the underlying molecular mechanism of SPX, the phosphorylation levels of signaling molecules were examined via western blot analysis. Moreover, in vivo bone regeneration by SPX (0.5 and 1 µg/µl) was evaluated in a calvarial defect model. New bone formation was analyzed using micro-computed tomography (micro-CT) and histology.
resultsThe results indicated that cell proliferation was not affected by SPX. However, SPX significantly increased ALP activity, mineralization, and the expression of genes for osteogenic differentiation markers, including runt-related transcription factor 2 (Runx2), Alp, collagen alpha-1(I) chain (Col1a1), osteocalcin (Oc), and bone sialoprotein (Bsp). In contrast, SPX downregulated the expression of ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1). Moreover, SPX upregulated phosphorylated mitogen-activated protein kinase kinase (MEK1/2) and extracellular signal-regulated kinase (ERK1/2). In vivo studies, micro-CT and histologic analysis revealed that SPX markedly increased a new bone formation.
conclusionOverall, these results demonstrated that SPX stimulated osteogenic differentiation in vitro and increased in vivo bone regeneration via the MEK/ERK pathway.
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