ArticleMolecular medicine (Cambridge, Mass.)2024
Integrin αVβ3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis.
Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Angiogenesis in ossification of the posterior longitudinal ligament: progress from mechanism to targeted intervention.Frontiers in cell and developmental biology · 2026Review
- Integrin-mediated SPP1 signaling from macrophages orchestrates extracellular matrix remodeling and chondrogenesis in heterotopic ossification.Journal of translational medicine · 2025Article
- Angiogenesis in rheumatoid Arthritis: Pathological characterization, pathogenic mechanisms, and nano-targeted therapeutic strategies.Bioactive materials · 2025Review
- Novel homozygous frameshift mutation of ITGB3 in the Glanzmann thrombasthenia patient with abnormal bone metabolism and congenital bone defects.Orphanet journal of rare diseases · 2025Article
- Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease.Molecular medicine (Cambridge, Mass.) · 2024Article
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Abstract
backgroundOssification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVβ3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVβ3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVβ3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL.
methodsOPLL or control ligament samples were collected in surgery. For OPLL samples, RNA-sequencing results revealed activation of the integrin family, particularly integrin αVβ3. Integrin αVβ3 expression was detected by qPCR, Western blotting, and immunohistochemical analysis. Fluorescence microscopy was used to observe the targeted inhibition of integrin αVβ3 by the c(RGDyk) peptide on ligaments fibroblasts (LFs) derived from patients with OPLL and endothelial cells (ECs). The effect of c(RGDyk) peptide on the ossification of pathogenic LFs was detected using qPCR, Western blotting. Alkaline phosphatase staining or alizarin red staining were used to test the osteogenic capability. The effect of the c(RGDyk) peptide on angiogenesis was determined by EC migration and tube formation assays. The effects of the c(RGDyk) peptide on heterotopic bone formation were evaluated by micro-CT, histological, immunohistochemical, and immunofluorescence analysis in vivo.
resultsThe results indicated that after being treated with c(RGDyk), the osteogenic differentiation of LFs was significantly decreased. Moreover, the c(RGDyk) peptide inhibited the migration of ECs and thus prevented the nutritional support required for osteogenesis. Furthermore, the c(RGDyk) peptide inhibited ectopic bone formation in mice. Mechanistic analysis revealed that c(RGDyk) peptide could inhibit osteogenesis and angiogenesis in OPLL by targeting integrin αVβ3 and regulating the FAK/ERK pathway.
conclusionsTherefore, the integrin αVβ3 appears to be an emerging therapeutic target for OPLL, and the c(RGDyk) peptide has dual inhibitory effects that may be valuable for the new therapeutic strategy of OPLL.
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