Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mesenchymal stem cells (MSCs) have been isolated from the pulp tissue of permanent teeth (dental pulp stem cells or DPSCs) and deciduous teeth (stem cells from human exfoliated deciduous teeth). We recently discovered another type of MSCs in the apical papilla of human immature permanent teeth termed stem cells from the apical papilla (SCAP). Here, we further characterized the apical papilla tissue and stem cell properties of SCAP using histologic, immunohistochemical, and immunocytofluorescent analyses. We found that the apical papilla is distinctive to the pulp in terms of containing less cellular and vascular components than those in the pulp. Cells in the apical papilla proliferated 2- to 3-fold greater than those in the pulp in organ cultures. Both SCAP and DPSCs were as potent in osteo/dentinogenic differentiation as MSCs from bone marrows, whereas they were weaker in adipogenic potential. The immunophenotype of SCAP is similar to that of DPSCs on the osteo/dentinogenic and growth factor receptor gene profiles. Double-staining experiments showed that STRO-1 coexpressed with dentinogenic markers such as bone sialophosphoprotein, osteocalcin, and growth factors FGFR1 and TGFbetaRI in cultured SCAP. Additionally, SCAP express a wide variety of neurogenic markers such as nestin and neurofilament M upon stimulation with a neurogenic medium. We conclude that SCAP are similar to DPSCs but a distinct source of potent dental stem/progenitor cells. Their implications in root development and apexogenesis are discussed.
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PMID:Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. 1821 74

Perfusion culture of osteoprogenitor cells seeded within porous scaffolds suitable for bone tissue engineering is known to enhance deposition of a bone-like extracellular matrix, and the underlying mechanism is thought to involve flow-induced activation of mechanotransductive signaling pathways. Basic studies have shown that mechanotransduction is enhanced by impulse flow and may be mediated through autocrine signaling pathways. To test this, an intermittent flow regimen (5 min on/5 min off ) that exerts impulses on adherent cells and permits accumulation of secreted factors in the cell microenvironment was compared to continuous flow for its ability to stimulate phosphorylation of ERK and p38, synthesis of prostaglandin E2 (PGE2), and expression of mRNA for collagen 1alpha1 (Col-1alpha1), osteopontin (OPN), bone sialoprotein (BSP), and osteocalcin (OCN). Studies were performed using bone marrow stromal cells cultured in osteogenic media, and parallel-plate flow chambers were used to exert a shear stress of 2.3 dyn/cm2 on cell layers. Results show that continuous flow significantly enhanced phosphorylation of ERK and p38 after 30 min relative to intermittent flow, while intermittent flow significantly increased accumulation of PGE2 in the circulating medium by 24 h relative to continuous flow. Neither continuous nor intermittent flow affected mRNA expression of Col-1alpha1 and OPN after 4 h, but when monolayers were stimulated for 24 h and then allowed to differentiate under static conditions for an additional 13 days, expression of Col-1alpha1, OPN, BSP, and OCN under continuous and intermittent flow was similar and significantly elevated relative to static controls. This study demonstrates that the variation of perfusion regimen modulates mechanotransductive signaling.
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PMID:Effect of intermittent shear stress on mechanotransductive signaling and osteoblastic differentiation of bone marrow stromal cells. 1835 27

Degradable synthetic polymers with a nanofibrous structure have shown great promise in populating and recruiting cells for the reconstruction of damaged tissues. However, poor cell affinity and lack of bioactivity have limited their potential usefulness in bone regeneration. We produced polymeric nanofiber poly(epsilon-caprolactone) (PCL) with its surface mineralized with bone-like apatite for use as bone regenerative and tissue engineering matrices. PCL was first electrospun into a nanofibrous web, and the surface was further mineralized with apatite following a series of solution treatments. The surface of the mineralized PCL nanofiber was observed to be almost fully covered with nanocrystalline apatites. Through mineralization, the wettability of the nanofiber matrix was greatly improved. Moreover, the murine-derived osteoblastic cells were shown to attach and grow actively on the apatite-mineralized nanofibrous substrate. In particular, the mineralized PCL nanofibrous substrate significantly stimulated the expression of bone-associated genes, including Runx2, collagen type I, alkaline phosphatase, and osteocalcin, when compared with the pure PCL nanofiber substrate without mineralization. The currently developed polymer nanofibrous web with the bioactive mineralized surface is considered to be potentially useful as bone regenerative and tissue engineering matrices.
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PMID:Apatite-mineralized polycaprolactone nanofibrous web as a bone tissue regeneration substrate. 1835 62

Low intensity pulsed ultrasound is used in the clinical treatment of fractures and other osseous defects. Level I clinical studies demonstrate the ability of a specific ultrasound signal (1.5 MHz ultrasound pulsed at 1 kHz, 20% duty cycle, 30 mW/cm(2) intensity (SATA)) to accelerate the healing time in fresh tibia, radius and scaphoid fractures by up to 40%. Additionally, the same ultrasound signal has been shown to be effective at resolving all types of nonunions of all ages, following a wide range of fracture types and primary fracture management techniques. Recently, significant efforts have resulted in a more comprehensive understanding of the biological mechanism of action that produces the documented clinical outcomes. Low intensity pulsed ultrasound has been demonstrated to accelerate in vivo all stages of the fracture repair process (inflammation, soft callus formation, hard callus formation). In particular, accelerated mineralisation has been demonstrated in vitro with increases in osteocalcin, alkaline phosphatase, VEGF and MMP-13 expression. Integrins, a family of mechanoreceptors present on a wide range of cells involved in the fracture healing process, have been shown to be activated by the ultrasound signal. Downstream of the integrin activation, focal adhesions occur on the surface of cells with the activation of multiple signalling pathways, including the ERK, NF-kappabeta, and PI3 kinase pathways. These pathways have been directly linked to the production of COX-2 and prostaglandin, which are key to the processes of mineralisation and endochondral ossification in fracture healing.
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PMID:Low intensity pulsed ultrasound for fracture healing: a review of the clinical evidence and the associated biological mechanism of action. 1848 59

Critical-sized defects in bone, whether caused by cancer tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold-standard treatment for bone repair. The primary purpose of a tissue-engineered scaffold is to incite and promote the natural healing process of bone, which does not occur in critical-sized defects. In this work, a solvent-free template synthesis technique was utilized to fabricate uniform arrays of substrate-bound poly(epsilon-caprolactone) (PCL) nanowires. Biodegradation of PCL nanowire surfaces was characterized using scanning electron microscopy (SEM) and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. Rat bone marrow-derived mesenchymal stem cells (MSCs) were employed to assess short-term biocompatibility and long-term bioactivity of nanowire surfaces. Short-term cell studies indicated that PCL nanowire surfaces supported enhanced cell adhesion and viability compared with control surfaces. MSCs seeded on nanowire surfaces also displayed increased levels of alkaline phosphatase (ALP) after 1, 2, and 3 weeks in culture. Calcium-phosphate mineralization was substantially accelerated on nanowire surfaces compared to control surfaces as indicated through calcium staining, von Kossa staining, SEM, and electron dispersive spectroscopy (EDS). Increased levels of inter- and extracellular levels of osteocalcin and osteopontin were observed on nanowire surfaces using immunofluorescence techniques after 3 weeks of culture. Considering the simplicity of the presented fabrication technique, capacity for solvent-free encapsulation of bioactive molecules or particles, and enhanced MSC performance on nanowire surfaces, this work presents an excellent foundation for the development of 3-D scaffolds for bone tissue regeneration.
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PMID:Biodegradable poly(epsilon-caprolactone) nanowires for bone tissue engineering applications. 1901 62

Concerns over utilizing autogenous cancellous bone grafts (such as donor-site morbidity, increased surgical time/complication rate, and restricted availability) as the gold-standard treatment for critical-sized defects in bone have motivated the development of a wide variety of sophisticated synthetic bone scaffolds in recent years. In this work, a novel solvent-free template synthesis technique was utilized to fabricate poly(epsilon-caprolactone) (PCL) nanowire surfaces as a building block for the development of three-dimensional bone scaffolds. Bone marrow-derived mesenchymal stem cells (MSCs) were used to characterize the short- and long-term in vitro biocompatibility and cellular response to these surfaces. A 4-week study in rats was conducted to assess in vivo biocompatibility as well. Short-term in vitro studies revealed that PCL nanowire surfaces enhanced MSC response in terms of survivability, viability, cytoskeleton changes, and morphology as compared with control surfaces (smooth PCL and polystyrene). In long-term in vitro studies, nanowire surfaces induced a rapid production of bone extracellular matrix by differentiated MSCs as indicated by accelerated calcium phosphate mineralization, and osteocalcin and osteopontin production. In vivo studies and histological analysis confirmed that nanowire surfaces are biocompatible. Preliminary biodegradation studies were conducted and indicated that rate of PCL biodegradation can, to some extent, be controlled through the inclusion of nanowires and ester-degrading enzymes. In addition to demonstrating enhanced short- and long-term MSC response to PCL nanowire surfaces, this work presents a simple technique for solvent-free fabrication and bioactive molecule encapsulation of biocompatible, biodegradable three-dimensional bone scaffold components and warrants further investigation.
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PMID:Biocompatibility and mesenchymal stem cell response to poly(epsilon-caprolactone) nanowire surfaces for orthopedic tissue engineering. 1932 68

Although substance P (SP) is associated with osteoclast differentiation and bone resorption, little is known about the osteogenic differentiation-inducing effects of SP in periodontal ligament (PDL) cells. This study investigated whether PDL cells could differentiate into osteoblastic-like cells by SP. The expression of osteoblastic differentiation markers such as osteopontin (OPN), osteonectin (ON), osteocalcin (OCN) and bone sialoprotein (BSP) were evaulated by Western blotting. Additionally, SP-mediated heme oxygenase-1 (HO-1) pathways were further clarified. SP increased HO-1 and osteogenic differentiation in concentration- and time-dependent manners, as determined by OPN, ON, OCN and BSP expression. Furthermore, treatment with inhibitors of p38, ERK MAPK, and NF-kappaB abolished SP-induced osteogenic differentiation and HO-1 expression. SP-induced translocation of Nrf-2 was also observed. The combined results suggest that SP activates the stress-response enzymes HO-1 and Nrf-2, subsequently leading to upregulation of osteogenic differentiation in human PDL cells.
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PMID:Effects of substance P on osteoblastic differentiation and heme oxygenase-1 in human periodontal ligament cells. 1935 3

In this study, poly (epsilon-caprolactone) [PCL] and its collagen composite blend (PCL/Col) were fabricated to scaffolds using electrospinning method. Incorporated collagen was present on the surface of the fibers, and it modulated the attachment and proliferation of pig bone marrow mesenchymal cells (pBMMCs). Osteogenic differentiation markers were more pronounced when these cells were cultured on PCL/Col fibrous meshes, as determined by immunohistochemistry for collagen type I, osteopontin, and osteocalcin. Matrix mineralization was observed only on osteogenically induced PCL/Col constructs. Long bone analogs were created by wrapping osteogenic cell sheets around the PCL/Col meshes to form hollow cylindrical cell-scaffold constructs. Culturing these constructs under dynamic conditions enhanced bone-like tissue formation and mechanical strength. We conclude that electrospun PCL/Col mesh is a promising material for bone engineering applications. Its combination with osteogenic cell sheets offers a novel and promising strategy for engineering of tubular bone analogs.
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PMID:Composite electrospun scaffolds for engineering tubular bone grafts. 1952 83

The aim of current study is to investigate the in vitro and in vivo behavior of dental pulp stem cells (DPSCs) seeded on electrospun poly(epsilon-caprolactone) (PCL)/gelatin scaffolds with or without the addition of nano-hydroxyapatite (nHA). For the in vitro evaluation, DNA content, alkaline phosphatase (ALP) activity and osteocalcin (OC) measurement showed that the scaffolds supported DPSC adhesion, proliferation, and odontoblastic differentiation. Moreover, the presence of nHA upregulated ALP activity and promoted OC expression. Real-time PCR data confirmed these results. SEM micrographs qualitatively confirmed the proliferation and mineralization characteristics of DPSCs on both scaffolds. Subsequently, both scaffolds seeded with DPSCs were subcutaneously implanted into immunocompromised nude mice. Scaffolds with nHA but without cells were implanted as control. Histological evaluation revealed that all implants were surrounded by a thin fibrous tissue capsule without any adverse effects. The cell/scaffold composites showed obvious in vivo hard tissue formation, but there was no sign of tissue ingrowth. Further, the combination of nHA in scaffolds did upregulate the expression of specific odontogenic genes. In conclusion, the incorporation of nHA in nanofibers indeed enhanced DPSCs differentiation towards an odontoblast-like phenotype in vitro and in vivo.
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PMID:The performance of dental pulp stem cells on nanofibrous PCL/gelatin/nHA scaffolds. 1955 87

The ERK/MAP kinase pathway is an important regulator of gene expression and differentiation in postmitotic cells. To understand how this pathway controls gene expression in bone, we examined the subnuclear localization of P-ERK in differentiating osteoblasts. Induction of differentiation was accompanied by increased ERK phosphorylation and expression of osteoblast-related genes, including osteocalcin (Bglap2) and bone sialoprotein (Ibsp). Confocal immunofluorescence microscopy revealed that P-ERK colocalized with the RUNX2 transcription factor in the nuclei of differentiating cells. Interestingly, a portion of this nuclear P-ERK was directly bound to the proximal promoter regions of Bglap2 and Ibsp. Furthermore, the level of P-ERK binding to chromatin increased with differentiation, whereas RUNX2 binding remained relatively constant. The P-ERK-chromatin interaction was seen only in RUNX2-positive cells, required intact RUNX2-selective enhancer sequences, and was blocked with MAPK inhibition. These studies show for the first time that RUNX2 specifically targets P-ERK to the chromatin of osteoblast-related genes, where it may phosphorylate multiple substrates, including RUNX2, resulting in altered chromatin structure and gene expression.
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PMID:Differentiation-dependent association of phosphorylated extracellular signal-regulated kinase with the chromatin of osteoblast-related genes. 1958 Apr 58


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