کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8645308 | 1569781 | 2018 | 40 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacological targeting of the mammalian clock reveals a novel analgesic for osteoarthritis-induced pain
ترجمه فارسی عنوان
هدف قرار دادن فارماکولوژیک ساعتهای پستانداران، یک ضد درد جدید برای درد ناشی از استئوآرتریت است
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کلمات کلیدی
DRGDFNPMMPTTRT-PCROARSIRev-erbPWTDFDdorsal root ganglion - گانگلیون ریشه پشتیBmal1 - BMAL1paw withdrawal threshold - آستانه برداشتن پاProbability - احتمالات، احتمالCircadian disruption - اختلال دورانیOsteoarthritis - استئوآرتریت(آرتروز)Osteoarthritis Research Society International - انجمن بین المللی تحقیقات استئوآرتریتintrathecal - اینتراکتالlight-dark - تیره روشن یا کمرنگ و پررنگstandard error of the mean - خطای استاندارد میانگینPain - دردHour - ساعتSEM - مدل معادلات ساختاری / میکروسکوپ الکترونی روبشیIntraarticular - مفصلی داخلdegree of freedom - میزان آزادیreal-time polymerase chain reaction - واکنش زنجیره ای پلیمراز واقعی در زمان واقعیClock gene - ژن ساعت
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
ژنتیک
چکیده انگلیسی
Environmental disruption of the circadian rhythm is linked with increased pain due to osteoarthritis (OA). We aimed to characterize the role of the clock gene in OA-induced pain more systemically using both genetic and pharmacological approaches. Genetically modified mice, (bmal1f/fNav1.8CreERT mice), generated by deleting the critical clock gene, bmal1, from Nav1.8 sensory neurons, were resistant to the development of mechanical hyperalgesia associated with OA induced by partial medial meniscectomy (PMM) of the knee. In wild-type mice, induction of OA by PMM surgery led to a substantial increase in BMAL1 expression in DRG neurons. Interestingly, pharmacological activation of the REV-ERB (a negative regulator of bmal1 transcription) with SR9009 resulted in reduction of BMAL1 expression, and a significant decrease in mechanical hyperalgesia associated with OA. Cartilage degeneration was also significantly reduced in mice treated with the REV-ERB agonist SR9009. Based on these data, we also assessed the effect of pharmacological activation of REV-ERB using a model of environmental circadian disruption with its associated mechanical hyperalgesia, and noted that SR9009 was an effective analgesic in this model as well. Our data clearly demonstrate that genetic disruption of the molecular clock, via deletion of bmal1 in the sensory neurons of the DRG, decreases pain in a model of OA. Furthermore, pharmacological activation of REV-ERB leading to suppression of BMAL1 expression may be an effective method for treating OA-related pain, as well as to reduce joint damage associated with this disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gene - Volume 655, 20 May 2018, Pages 1-12
Journal: Gene - Volume 655, 20 May 2018, Pages 1-12
نویسندگان
Vaskar Das, Ranjan Kc, Xin Li, Disha Varma, Sujun Qiu, Jeffrey S. Kroin, Christopher B. Forsyth, Ali Keshavarzian, Andre J. van Wijnen, Thomas J. Park, Gary S. Stein, Insug O-Sullivan, Thomas P. Burris, Hee-Jeong Im,