scholarly journals Repercussion of nonsteroidal anti-inflammatory drugs on the gene expression of human osteoblasts

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5415 ◽  
Author(s):  
Lucia Melguizo-Rodríguez ◽  
Víctor J. Costela-Ruiz ◽  
Francisco J. Manzano-Moreno ◽  
Rebeca Illescas-Montes ◽  
Javier Ramos-Torrecillas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transforming Growth Factor ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Related Transcription Factor ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
And Function ◽  
Osteoblast Maturation

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used in clinical practice, which can have adverse effects on the osteoblast. The objective of this study was to determine the effect of NSAIDs on the osteoblast by analyzing the gene expression of different markers related to osteoblast maturation and function when treated in vitro with different NSAIDs. Methods Three human osteoblast lines from bone samples of three healthy volunteers were treated with 10 µM acetaminophen, indomethacin, ketoprofen, diclofenac, ibuprofen, ketorolac, naproxen, and piroxicam. The gene expression of different markers (run related transcription factor 2 [RUNX-2], type 1 collagen [COL-I], osterix [OSX], osteocalcin [OSC], bone morphogenetic protein 2 [BMP-2] and 7 [BMP-7], transforming growth factor β1 [TGF-β1], and TGFβ receptors [TGFβR1, TGFβR2; TGFBR3]) were analyzed by real-time PCR at 24 h of treatment. Results Expression of RUNX-2, COL-I, OSX, was reduced by treatment with all studied NSAIDs, OSC expression was reduced by all NSAIDs except for ketoprofen, naproxen, or piroxicam. Expression of BMP-7 was reduced by all NSAIDs; BMP-2 was reduced by all except for naproxen. In general, NSAID treatment increased the expression of TGF-β1, but not of its receptors (TGFβ-R1, TGFβ-R2, andTFGβ-R3), which was either unchanged or reduced by the treatment. Conclusion These data confirm that NSAIDs can affect osteoblast physiology, suggesting their possible impact on bone.

Targeting EZH2 Ameliorates the LPS-Inhibited PDLSC Osteogenesis via Wnt/β-Catenin Pathway

2021 ◽  
pp. 1-9
Author(s):  
Mosha Cheng ◽  
Qing Zhou
Keyword(s):  
Bone Morphogenetic Protein 2 ◽  
Periodontal Ligament Stem Cells ◽  
Alizarin Red ◽  
Protein Levels ◽  
Inflammatory Conditions ◽  
Morphogenetic Protein ◽  
Related Transcription Factor ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Osteoblast Maturation

As a histone methyltransferase, enhancer of zeste homolog 2 (EZH2), suppresses osteoblast maturation and is involved in inflammation. However, the role of EZH2 in human periodontal ligament stem cells (PDLSCs) under inflammation still needs to be further investigated. This study aimed to identify the underlying mechanisms and explore the function of EZH2 in PDLSC osteogenesis under inflammation. PDLSCs were treated with sh-EZH2, DZNep or DKK1 under inflammation. The alkaline phosphatase (ALP) activity, alizarin red staining, and osteogenesis-related protein levels were analyzed. Lipopolysaccharide (LPS)-induced inflammation restrained osteogenic differentiation. Under inflammation, the upregulation of EZH2 suppressed the expression of osteogenic markers, including osteocalcin, runt-related transcription factor 2, and bone morphogenetic protein-2, the activity of ALP, and the accumulation of mineralization through the Wnt/β-catenin pathway. EZH2 knockdown inhibited the levels of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. These results suggested that LPS-induced overexpression of EZH2 suppressed PDLSC osteogenesis under inflammatory conditions through the Wnt/β-catenin pathway. These findings give new insights into the physiological differentiation and pathological inflammation of PDLSC osteogenesis, and provide an underlying therapeutic target for periodontitis.

scholarly journals Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation

2010 ◽  
Vol 190 (6) ◽  
pp. 1107-1121 ◽  
Author(s):  
Harikiran Nistala ◽  
Sui Lee-Arteaga ◽  
Silvia Smaldone ◽  
Gabriella Siciliano ◽  
Luca Carta ◽  
...  
Keyword(s):  
Bone Formation ◽  
Transforming Growth Factor ◽  
Bone Mineralization ◽  
Bmp Signaling ◽  
Direct Role ◽  
Morphogenetic Protein ◽  
Fibrillin 1 ◽  
Osteoblast Maturation

Extracellular regulation of signaling by transforming growth factor (TGF)–β family members is emerging as a key aspect of organ formation and tissue remodeling. In this study, we demonstrate that fibrillin-1 and -2, the structural components of extracellular microfibrils, differentially regulate TGF-β and bone morphogenetic protein (BMP) bioavailability in bone. Fibrillin-2–null (Fbn2−/−) mice display a low bone mass phenotype that is associated with reduced bone formation in vivo and impaired osteoblast maturation in vitro. This Fbn2−/− phenotype is accounted for by improper activation of latent TGF-β that selectively blunts expression of osterix, the transcriptional regulator of osteoblast maturation, and collagen I, the structural template for bone mineralization. Cultured osteoblasts from Fbn1−/− mice exhibit improper latent TGF-β activation as well, but mature faster because of increased availability of otherwise matrix-bound BMPs. Additional in vitro evidence excludes a direct role of microfibrils in supporting mineral deposition. Together, these findings identify the extracellular microfibrils as critical regulators of bone formation through the modulation of endogenous TGF-β and BMP signaling.

scholarly journals Bioactivity of a Novel Polycaprolactone-Hydroxyapatite Scaffold Used as a Carrier of Low Dose BMP-2: An In Vitro Study

Polymers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 466
Author(s):  
Pawornwan Rittipakorn ◽  
Nuttawut Thuaksuban ◽  
Katanchalee Mai-ngam ◽  
Satrawut Charoenla ◽  
Warobon Noppakunmongkolchai
Keyword(s):  
In Vitro Study ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Cell Scaffold ◽  
Related Transcription Factor ◽  
Group A ◽  
In Vitro Response ◽  
Hydroxyapatite Scaffold ◽  
Group B

Scaffolds of polycaprolactone-30% hydroxyapatite (PCL-30% HA) were fabricated using melt stretching and multilayer deposition (MSMD), and the in vitro response of osteoblasts to the scaffolds was assessed. In group A, the scaffolds were immersed in 10 µg/mL bone morphogenetic protein-2 (BMP-2) solution prior to being seeded with osteoblasts, and they were cultured in the medium without BMP-2. In group B, the cell-scaffold constructs without BMP-2 were cultured in medium containing 10 µg/mL BMP-2. The results showed greater cell proliferation in group A. The upregulation of runt-related transcription factor 2 and osteocalcin genes correlated with the release of BMP-2 from the scaffolds. The PCL-30% HA MSMD scaffolds appear to be suitable for use as osteoconductive frameworks and BMP-2 carriers.

scholarly journals Degeneration of Lumbar Intervertebral Discs: Characterization of Anulus Fibrosus Tissue and Cells of Different Degeneration Grades

2020 ◽  
Vol 21 (6) ◽  
pp. 2165
Author(s):  
Stefan Stich ◽  
Michal Jagielski ◽  
Anja Fleischmann ◽  
Carola Meier ◽  
Patricia Bussmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transforming Growth Factor ◽  
Cultured Cells ◽  
Transforming Growth Factor Β1 ◽  
Intervertebral Discs ◽  
Bone Morphogenetic Protein 2 ◽  
Anulus Fibrosus ◽  
Morphogenetic Protein ◽  
Factor Α

Intervertebral disc (IVD) herniation and degeneration is a major source of back pain. In order to regenerate a herniated and degenerated disc, closure of the anulus fibrosus (AF) is of crucial importance. For molecular characterization of AF, genome-wide Affymetrix HG-U133plus2.0 microarrays of native AF and cultured cells were investigated. To evaluate if cells derived from degenerated AF are able to initiate gene expression of a regenerative pattern of extracellular matrix (ECM) molecules, cultivated cells were stimulated with bone morphogenetic protein 2 (BMP2), transforming growth factor β1 (TGFβ1) or tumor necrosis factor-α (TNFα) for 24 h. Comparative microarray analysis of native AF tissues showed 788 genes with a significantly different gene expression with 213 genes more highly expressed in mild and 575 genes in severe degenerated AF tissue. Mild degenerated native AF tissues showed a higher gene expression of common cartilage ECM genes, whereas severe degenerated AF tissues expressed genes known from degenerative processes, including matrix metalloproteinases (MMP) and bone associated genes. During monolayer cultivation, only 164 differentially expressed genes were found. The cells dedifferentiated and altered their gene expression profile. RTD-PCR analyses of BMP2- and TGFβ1-stimulated cells from mild and severe degenerated AF tissue after 24 h showed an increased expression of cartilage associated genes. TNFα stimulation increased MMP1, 3, and 13 expression. Cells derived from mild and severe degenerated tissues could be stimulated to a comparable extent. These results give hope that regeneration of mildly but also strongly degenerated disc tissue is possible.

scholarly journals Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Hongsik Cho ◽  
Andrew Walker ◽  
Jeb Williams ◽  
Karen A. Hasty
Keyword(s):  
Gene Expression ◽  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Cyclooxygenase 2 ◽  
Cox Inhibitor ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory

Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-αwas incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxibin vivowas investigated using a posttraumatic OA (PTOA) mouse model.In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 productionin vitroand that celecoxib may demonstrate beneficial effects on anabolic metabolismin vivo.

scholarly journals Stimulation of Human Osteoblast Differentiation in Magneto-Mechanically Actuated Ferromagnetic Fibre Networks

2019 ◽  
Author(s):  
Galit Katarivas Levy ◽  
Mark A. Birch ◽  
Roger A. Brooks ◽  
Suresh Neelakantan ◽  
Athina E. Markaki
Keyword(s):  
Porous Scaffold ◽  
Bone Ingrowth ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Related Transcription Factor ◽  
Implantable Biomedical Devices ◽  
Experimental Use ◽  
Osteogenesis In Vitro

There is currently an interest in “active” implantable biomedical devices that include mechanical stimulation as an integral part of their design. This paper reports the experimental use of a porous scaffold made of interconnected networks of slender ferromagnetic fibres that can be actuated in vivo by an external magnetic field applying strains to in-growing cells. Such scaffolds have been previously characterized in terms of their mechanical and cellular responses. In this study, it is shown that the shape changes induced in the scaffolds can be used to promote osteogenesis in vitro. In particular, immunofluorescence, gene and protein analyses reveal that the actuated networks exhibit higher mineralization and extracellular matrix production, and express higher levels of osteocalcin, alkaline phosphatase, collagen type 1a1, runt-related transcription factor 2 and bone morphogenetic protein 2 than the static controls at the 3-week time point. The results suggest that the cells filling the inter-fibre spaces are able to sense and react to the magneto-mechanically induced strains facilitating osteogenic differentiation and maturation. This work provides evidence in support of using this approach to stimulate bone ingrowth around a device implanted in bone and can pave the way for further applications in bone tissue engineering.

scholarly journals Stimulation of Human Osteoblast Differentiation in Magneto-Mechanically Actuated Ferromagnetic Fiber Networks

2019 ◽  
Vol 8 (10) ◽  
pp. 1522 ◽  
Author(s):  
Galit Katarivas Levy ◽  
Mark A. Birch ◽  
Roger A. Brooks ◽  
Suresh Neelakantan ◽  
Athina E. Markaki
Keyword(s):  
Porous Scaffold ◽  
Bone Ingrowth ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Related Transcription Factor ◽  
Implantable Biomedical Devices ◽  
Experimental Use ◽  
Osteogenesis In Vitro

There is currently an interest in “active” implantable biomedical devices that include mechanical stimulation as an integral part of their design. This paper reports the experimental use of a porous scaffold made of interconnected networks of slender ferromagnetic fibers that can be actuated in vivo by an external magnetic field applying strains to in-growing cells. Such scaffolds have been previously characterized in terms of their mechanical and cellular responses. In this study, it is shown that the shape changes induced in the scaffolds can be used to promote osteogenesis in vitro. In particular, immunofluorescence, gene and protein analyses reveal that the actuated networks exhibit higher mineralization and extracellular matrix production, and express higher levels of osteocalcin, alkaline phosphatase, collagen type 1α1, runt-related transcription factor 2 and bone morphogenetic protein 2 than the static controls at the 3-week time point. The results suggest that the cells filling the inter-fiber spaces are able to sense and react to the magneto-mechanically induced strains facilitating osteogenic differentiation and maturation. This work provides evidence in support of using this approach to stimulate bone ingrowth around a device implanted in bone and can pave the way for further applications in bone tissue engineering.

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