Polydeoxyribonucleotide Ameliorates Inflammation and Apoptosis in Achilles Tendon-Injury Rats
2
조회
0
다운로드
7
인용
0
참고문헌
키워드
초록
Purpose: Adenosine A2A receptor agonist polydeoxyribonucleotide (PDRN) possesses an anti-inflammatory effect and suppress apoptotic cell death in several disorders. In this current study, the effect of PDRN on inflammation and apoptosis in rats with Achilles tendon injury was investigated. Methods: von Frey filament test and plantar test were conducted for the determination of pain threshold. Analysis of histological alterations was conducted by hematoxylin and eosin staining. Immunohistochemistry for cleaved caspase-3-positive cells and cleaved caspase-9-positive cells was done. Enzyme-linked immunoassay was used to detect the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and cyclic adenosine-3’,5’-monophosphate (cAMP). Western blot was conducted to detect the protein levels of cAMP response element-binding protein (CREB), protein kinase A (PKA), Bcl-2-associated X (Bax), and B-cell lymphoma 2 (Bcl-2). Results: PDRN treatment relieved mechanical allodynia and alleviated thermal hyperalgesia after Achilles tendon injury. TNF-α and IL-6 concentrations were decreased by PDRN application. PDRN injection significantly enhanced cAMP concentration and phosphorylated CREB versus CREB ratio, showing cAMP-PKA-CREB pathway was activated by PDRN application. PDRN treatment inhibited percentages of cleaved caspase-3-positive cells and caspase-9-posiive cells and the suppressed Bax versus Bcl-2 ratio in Achilles tendon injury rats. Conclusions: PDRN is probably believed to have a good effect on pain and inflammation in the urogenital organs. PDRN may be used as a new treatment for Achilles tendon injury.
Abstract
Purpose: Adenosine A2A receptor agonist polydeoxyribonucleotide (PDRN) possesses an anti-inflammatory effect and suppress apoptotic cell death in several disorders. In this current study, the effect of PDRN on inflammation and apoptosis in rats with Achilles tendon injury was investigated. Methods: von Frey filament test and plantar test were conducted for the determination of pain threshold. Analysis of histological alterations was conducted by hematoxylin and eosin staining. Immunohistochemistry for cleaved caspase-3-positive cells and cleaved caspase-9-positive cells was done. Enzyme-linked immunoassay was used to detect the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and cyclic adenosine-3’,5’-monophosphate (cAMP). Western blot was conducted to detect the protein levels of cAMP response element-binding protein (CREB), protein kinase A (PKA), Bcl-2-associated X (Bax), and B-cell lymphoma 2 (Bcl-2). Results: PDRN treatment relieved mechanical allodynia and alleviated thermal hyperalgesia after Achilles tendon injury. TNF-α and IL-6 concentrations were decreased by PDRN application. PDRN injection significantly enhanced cAMP concentration and phosphorylated CREB versus CREB ratio, showing cAMP-PKA-CREB pathway was activated by PDRN application. PDRN treatment inhibited percentages of cleaved caspase-3-positive cells and caspase-9-posiive cells and the suppressed Bax versus Bcl-2 ratio in Achilles tendon injury rats. Conclusions: PDRN is probably believed to have a good effect on pain and inflammation in the urogenital organs. PDRN may be used as a new treatment for Achilles tendon injury.
참고문헌 (27)
- Dakin SG, "Chronic inflammation is a feature of Achilles tendinopathy and rupture", Br J Sports Med, 52, pp.359~367 (2018)
- Jeong C, "Exploring the in vivo anti-inflammatory actions of simvastatin-loaded porous microspheres on inflamed tenocytes in a collagenase-induced animal model of Achilles tendinitis", Int J Mol Sci, 19, pp.E820~ (2018)
- Pearce CJ, "Is apoptosis the cause of noninsertional achilles tendinopathy?", Am J Sports Med, 37, pp.2440~2444 (2009)
- Inoue S, "Ordering of caspases in cells undergoing apoptosis by the intrinsic pathway", Cell Death Differ, 16, pp.1053~1061 (2009)
- 김유미, "Treadmill exercise with bone marrow stromal cells transplantation facilitates neuroprotective effect through BDNF-ERK1", 2 pathway in spinal cord injury rats, 2018, pp.14(3), 335~340[DOI]
- Upadhyay D, "Particulate matter induces alveolar epithelial cell DNA damage and apoptosis : role of free radicals and the mitochondria", Am J Respir Cell Mol Biol, 29, pp.180~187 (2003)
- Bell R, "Inhibition of apoptosis exacerbates fatigue-damage tendon injuries in an in vivo rat model", Eur Cell Mater, 36, pp.44~56 (2018)
- 고일규, "Late starting treadmill exercise improves spatial leaning ability through suppressing CREP", BDNF, Journal of exercise rehabilitation, pp.2018, 14(3)[DOI]
- Odashima M, "Activation of A2A adenosine receptor attenuates intestinal inflammation in animal models of inflammatory bowel disease", Gastroenterology, 129, pp.26~33 (2005)
- Veronesi F, "Polydeoxyribonucleotides(PDRNs)from skin to musculoskeletal tissue regeneration via adenosine A2A receptor involvement", J Cell Physiol, 232, pp.2299~2307 (2017)
- Ko IG, "Combination therapy with polydeoxyribonucleotide and proton pump inhibitor enhances therapeutic effectiveness for gastric ulcer in rats", Life Sci, 203, pp.12~19 (2018)
- 전정원, "Adenosine A2A-receptor agonist polydeoxyribonucleotide promotes gastric ulcer healing in Mongolian gerbils", Animal Cells and Systems, 18(6), pp.399~406 (2014), 한국통합생물학회[DOI]
- An J, "Polydeoxyribonucleotide ameliorates lipopolysaccharide-induced lung injury by inhibiting apoptotic cell death in rats", Int J Mol Sci, 18, pp.E1847~ (2017)
- Freedman BR, "Biomechanical and structural response of healing Achilles tendon to fatigue loading following acute injury", J Biomech, 47, pp.2028~2034 (2014)
- Kang SH, "Polydeoxyribonucleotide improves tendon healing following achilles tendon injury in rats", J Orthop Res, 36, pp.1767~1776 (2018)
- Dixon WJ, "Staircase bioassay : the up-and-down method", Neurosci Biobehav Rev, 15, pp.47~50 (1991)
- Zhou C, "Electrophysiological characterization of spinal neuron sensitization by elevated calcium channel α-2-δ-1 subunit protein", Eur J Pain, 18, pp.649~658 (2014)
- Le Bars D, "Animal models of nociception", Pharmacol Rev, 53, pp.597~652 (2001)
- 박상서, "Effect of sildenafil citrate on brain central fatigue after exhaustive swimming exercise in rats", Journal of exercise rehabilitation, 15(5), pp.651~656 (2019), 한국운동재활학회[DOI]
- 송상혁, "Treadmill exercise and wheel exercise improve motor function by suppressing apoptotic neuronal cell death in brain inflammation rats", Journal of exercise rehabilitation, 14(6), pp.911~919 (2018), 한국운동재활학회
- 김미아, "Berberine Ameliorates Brain Inflammation in Poloxamer 407-Induced Hyperlipidemic Rats", International Neurourology Journal, 23, pp.102~110 (2019), 대한배뇨장애요실금학회[DOI]
- Christensen J, "Protease-activated receptors in the Achilles tendon-a potential explanation for the excessive pain signalling in tendinopathy", Mol Pain, 11, pp.13~ (2015)
- Deuis JR, "Methods used to evaluate pain behaviors in rodents", Front Mol Neurosci, 10, pp.284~ (2017)
- Haskó G, "Adenosine receptors : therapeutic aspects for inflammatory and immune diseases", Nat Rev Drug Discov, 7, pp.759~770 (2008)
- Han JH, "Anti-inflammatory effect of polydeoxyribonucleotide on zoledronic acidpretreated and lipopolysaccharide-stimulated RAW 264.7 cells", Exp Ther Med, 16, pp.400~405 (2018)
- Lui PP, "Increased apoptosis at the late stage of tendon healing", Wound Repair Regen, 15, pp.702~707 (2007)
- 이재민, "Treadmill exercise improves memory function by inhibiting hippocampal apoptosis in pilocarpine-induced epileptic rats", Journal of exercise rehabilitation, 14(5), pp.713~723 (2018), 한국운동재활학회