Harnessing and Modulating Inflammation in Strategies for Bone Regeneration

Mountziaris, Paschalia M.; Spicer, Patrick P.; Kasper, F. Kurtis; Mikos, Antonios G.

doi:10.1089/ten.teb.2011.0182

Cited by 186 publications

(209 citation statements)

References 107 publications

(156 reference statements)

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“…Removal of the hematoma significantly attenuates fracture repair as well. A growing body of evidence indicates that the signaling cascades initiated during the week-long acute inflammatory response plays an essential role in healing after fracture (21,22). Thus, fracture-hematoma and inflammation are required for fracture healing.…”

Section: Discussionmentioning

confidence: 99%

Ankaferd Blood Stopper: Does it have a role in fracture healing?

Aygül¹,

Topuz

Okay³

et al. 2013

Turk J Med Sci

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High-pressure and ultrahigh-pressure metamorphic rocks crop out widely in the northern Aegean. In many instances their ages and tectonic setting are poorly constrained. Here we report newly discovered high-pressure rocks of continental crustal origin and of Late Cretaceous age southwest of the Marmara Sea. Th ey occur at the contact between the Rhodope-Strandja Zone in the north and the Sakarya Zone in the south.Th e Kemer Metamorphic Complex is composed mainly of mica schist, calcschist and marble with minor metabasite and serpentinite. Th e mica schists contain garnet, phengite (3.30-3.44 c.p.f.u), (±) paragonite, albite, epidote, calcite, chlorite and titanite. Th e high-pressure metamorphic origin of the mica schists is shown by the high silica contents of the white micas and by glaucophane inclusions in garnet. In the metabasites the mineral assemblage is garnet, barroisite, epidote, albite, titanite, quartz, phengite and chlorite; no evidence is left for the former presence of high-pressure minerals. Metamorphic conditions are constrained by mineral equilibria: a 560-640°C temperature at a minimum pressure of 10 kbar. Th e metamorphism is dated at 64-84 Ma by the Rb-Sr phengite-whole rock method.Th e Kemer Metamorphic Complex is in tectonic contact with an accretionary ophiolitic mélange consisting of limestone, basalt, serpentinite, greywacke, radiolarian chert and metabasite. Some of the metabasites in the mélange contain Na-amphibole and lawsonite, indicating a subduction origin. Th e ages of the limestone blocks in the mélange range from Late Triassic to Late Cretaceous and that of the radiolarite blocks from Middle Jurassic to Early Cretaceous, indicating an oceanic domain dating back to Late Triassic at least. Th e Kemer Metamorphic Complex and the Çetmi Mélange are intruded by a granodiorite of Early Eocene (52 Ma) age and are unconformably covered by a Late Eocene volcano-sedimentary succession.Th e lithology of the Kemer Metamorphic Complex resembles a continental margin rather than an oceanic accretionary complex. Th is and the presence of a Late Cretaceous magmatic arc in the north (Sredna-Gora-Pontide) suggest that the Kemer metamorphic rocks were initially deposited on the northern passive margin of the Sakarya Zone, which was subducted under the Rhodope-Strandja continental domain.

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Section: Discussionmentioning

confidence: 99%

Ankaferd Blood Stopper: Does it have a role in fracture healing?

Aygül¹,

Topuz

Okay³

et al. 2013

Turk J Med Sci

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“…Because vascularization is essential for bone regeneration, angiogenic factors VEGF, PDGF, FGF and IGF are also being extensively tested for their usefulness in bone repair [18][19][20][21][22][23][24]. Immunomodulatory and anti-inflammatory agents, such as selective anti-cytokine therapies, corticosteroids and non-steroidal anti-inflammatory drugs, are used to direct specific effects on the regeneration and resorption pathways during bone healing [25,26]. Additionally, the use of parathyroidal hormone (PTH), growth hormone, steroids, calcitonin and vitamin D in systemic applications has also been shown to advance bone healing through stimulating osteogenesis, angiogenesis and osteoblast differentiation [27][28][29][30].…”

Section: Biomoleculesmentioning

confidence: 99%

“…Advanced hydrogels, naturally derived collagen and gelatin gels as well as synthetic polyethylene glycol and poly-vinyl alcohol-based hydrogels, serve as matrices for other products and mimic the extracellular matrix topography [74][75][76]. Biomaterials with immunomodulatory strategies, such as artificial extracellular matrices (ECMs) (hydrogels, ECM coatings) and materials with surface property modulation, have the ability to modify the immune function and improve bone repair and regeneration [25,77].…”

Section: Biomaterialsmentioning

confidence: 99%

The rational use of animal models in the evaluation of novel bone regenerative therapies

Perić¹,

Dumić-Čule²,

Grčević³

et al. 2015

Bone

117

116

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“…The normal physiological inflammatory reaction is one of the body's principal defense reactions, which is beneficial to fracture healing (3,4). However, chronic inflammation caused by infection or other factors, is detrimental to fracture healing (5,6).…”

Section: Introductionmentioning

confidence: 99%

Triptolide inhibits the function of TNF-α in osteoblast differentiation by inhibiting the NF-κB signaling pathway

Liu

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Chronic inflammation often delays fracture healing or leads to bone nonunion. Effectively suppressing pathological inflammation is crucial for fracture healing or bone remodeling. Triptolide, which is a diterpenoid epoxide, is the major active component of the Thunder God Vine, Tripterygium wilfordii. The aim of the present study was to investigate the role of triptolide in osteoblast differentiation and explore the molecular mechanisms of triptolide in fracture healing. Alkaline phosphatase (ALP) activity was used to evaluate osteoblast differentiation. ALP activity was measured via histochemical staining and western blotting was used to determine the expression of factors associated with inflammation. C2C12 cells were initially treated with 200 ng/ml bone morphogenetic protein (BMP)-2 alone for 3 days, which caused a significant increase in ALP activity (P<0.01). However, treatment with tumor necrosis factor (TNF)-α significantly decreased the ALP activity (P<0.05). Notably, treatment with the chronic inflammatory cytokine TNF-α significantly decreased the effect of BMP-2 in C2C12 cells compared with BMP-2 treatment alone (P<0.01). C2C12 cells were treated with increasing concentrations of BMP-2 or TNF-α for 3 days. The results demonstrated that TNF-α treatment significantly inhibited BMP-2-induced osteoblast differentiation in a dose-dependent manner (P<0.01). The role of triptolide in BMP-2-induced osteoblast differentiation was also examined. Cells were treated with BMP-2, BMP-2 + TNF-α alone, or BMP2 + TNF-α with increasing concentrations of triptolide (4, 8 or 16 ng/ml). After 3 days, the results of ALP activity revealed that triptolide significantly reversed the TNF-α-associated inhibition of osteoblast differentiation (P<0.01). Western blotting analysis demonstrated that triptolide markedly inhibited the phosphorylation of nuclear factor-κB, therefore suppressing the effects of TNF-α. In summary, triptolide is able to reverse the TNF-α-associated suppression of osteoblast differentiation, suggesting that triptolide treatment may have a positive effect on bone remodeling and fracture repairing.

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Harnessing and Modulating Inflammation in Strategies for Bone Regeneration

Cited by 186 publications

References 107 publications

Ankaferd Blood Stopper: Does it have a role in fracture healing?

Ankaferd Blood Stopper: Does it have a role in fracture healing?

The rational use of animal models in the evaluation of novel bone regenerative therapies

Triptolide inhibits the function of TNF-α in osteoblast differentiation by inhibiting the NF-κB signaling pathway

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