Protein kinase-like endoplasmic reticulum kinase (PERK) is a type I transmembrane protein located in the endoplasmic reticulum (ER). The PERK-eukaryotic initiation factor 2α (eIF2α)-activating transcription factor 4 (ATF4) pathway has been proved to be involved in osteoblast differentiation, but the involvement of the PERK-eIF2α-ATF4 signaling pathway in osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) has remained unclear. Therefore, the aim of this study was to explore the role of PERK in osteogenic differentiation of hPDLSCs and to assess whether PERK-eIF2α-ATF4 contributes to the process of osteogenic differentiation in hPDLSCs. In our study, we constructed PERK-overexpressed and PERK-silenced hPDLSCs by lentiviral transduction. Furthermore, lentivirus-transfected cells were induced to differentiate into osteoblast cells for different days. Alkaline phosphatase (ALP) activity and Alizarin Red staining were used to evaluate the mineralization capacity, and the expression levels of related genes-ATF4, ALP, bone sialoprotein, runt-related transcription factor 2 (Runx2), and osteocalcin were measured to evaluate the osteogenic differentiation of hPDLSCs. The results showed that over-expression of PERK greatly increased ALP activity and the expression levels of related osteogenic genes, which displayed the strongest osteogenesis capacity. However, suppression of PERK caused decreased ALP activity and the weakest osteogenesis capacity, and the levels of ATF4 and p-eIF2α in PERK-silenced hPDLSCs were also decreased. Our results indicated that the PERK gene plays an important role in the differentiation of hPDLSCs to osteoblast-like cells. The PERK-eIF2α-ATF4 signaling pathway contributes to osteoblast differentiation of hPDLSCs.
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http://dx.doi.org/10.1007/s10735-020-09863-y | DOI Listing |
ACS Appl Mater Interfaces
January 2025
School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China.
The involvement of neurons in the peripheral nervous system is crucial for bone regeneration. Mimicking extracellular matrix cues provides a more direct and effective strategy to regulate neuronal activity and enhance bone regeneration. However, the simultaneous coupling of the intrinsic mechanical-electrical microenvironment of implants to regulate innervated bone regeneration has been largely neglected.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address:
Periodontal disease is a major contributor to tooth loss worldwide in adults. Particularly, periodontal bone defect is a common clinical condition, yet current therapeutic strategies exhibit limited effectiveness. Recently, natural bone graft materials have attracted considerable interest for enhancing bone defect repair due to their superior biocompatibility and osteogenic capabilities.
View Article and Find Full Text PDFRegulatory T cells (Tregs) are increasingly being recognized for their role in promoting tissue repair. In this issue of the JCI, Chen et al. found that Tregs at the site of bone injury contribute to bone repair.
View Article and Find Full Text PDFElife
January 2025
Center for Medical Genetics Ghent, Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
Heritable fragile bone disorders (FBDs), ranging from multifactorial to rare monogenic conditions, are characterized by an elevated fracture risk. Validating causative genes and understanding their mechanisms remain challenging. We assessed a semi-high throughput zebrafish screening platform for rapid in vivo functional testing of candidate FBD genes.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
January 2025
British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, United Kingdom. (M.W., M.F., R.O., L.S., M.M., C.M.S.).
Background: The ECM (extracellular matrix) provides the microenvironmental niche sensed by resident vascular smooth muscle cells (VSMCs). Aging and disease are associated with dramatic changes in ECM composition and properties; however, their impact on the VSMC phenotype remains poorly studied.
Methods: Here, we describe a novel in vitro model system that utilizes endogenous ECM to study how modifications associated with age and metabolic disease impact the VSMC phenotype.
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