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Effects of dihydrotestosterone on osteoblast activity in curdlan-administered SKG mice and osteoprogenitor cells in patients with ankylosing spondylitis

التفاصيل البيبلوغرافية
العنوان: Effects of dihydrotestosterone on osteoblast activity in curdlan-administered SKG mice and osteoprogenitor cells in patients with ankylosing spondylitis
المؤلفون: Sungsin Jo, Jeehee Youn, Tae Hwan Kim, Ye Soo Park, Seunghun Lee, Bora Nam, Eunju Lee, Juyeon Kang, Yong-Gil Kim
المصدر: Arthritis Research & Therapy
Arthritis Research & Therapy, Vol 22, Iss 1, Pp 1-7 (2020)
سنة النشر: 2019
مصطلحات موضوعية: 0301 basic medicine, Male, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, beta-Glucans, Osteoprogenitors, medicine.medical_treatment, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Spinal ankylosis, Internal medicine, medicine, Animals, Humans, Spondylitis, Ankylosing, Testosterone, Osteoblastic activity, 030203 arthritis & rheumatology, Ankylosing spondylitis, Osteoblasts, Curdlan-administered SKG mice, biology, business.industry, Osteoblast, Dihydrotestosterone, Dutasteride, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Cytokine, Endocrinology, chemistry, Osteocalcin, biology.protein, Sclerostin, lcsh:RC925-935, business, medicine.drug, Research Article
الوصف: Background Ankylosing spondylitis (AS) is characteristically male-predominant, and progressive spinal ankylosis affects male patients more severely; however, the hormonal effects in males with AS are poorly understood. Methods In the present study, the regulatory effects of dutasteride, a 5-α reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone (DHT), were examined in curdlan-administered male SKG mice to determine spinal bone formation, bone metabolism-related markers, and interleukin (IL)-17A cytokine and T cell populations. In addition, the effects of DHT on primary osteoprogenitors from the facet joints of AS patients were assessed based on osteoblast-related parameters. DHT level was measured, and the correlation with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was analyzed in AS patients. Results In curdlan-administered SKG mice, dutasteride treatment resulted in an increased accumulation of hydroxyapatite in the spine which was positively correlated with serum IL-17A levels. In the analysis of bone metabolism-related molecules, a decrease in sclerostin levels was observed in the sera in the dutasteride group. Continuous exposure to DHT resulted in fewer calcium deposits in AS osteoprogenitors during osteoblast differentiation. DHT-treated AS osteoprogenitors showed decreased osteocalcin and increased DKK1 and SOST1 mRNA expression, supporting the results of the in vivo experiments. Treatment with dutasteride upregulated bone formation in the spine of curdlan-administered SKG mice and DHT treatment downregulated osteoblast differentiation in vitro. Conclusions Treatment with dutasteride affected the bone formation in the spine of curdlan-treated SKG mice, and DHT treatment attenuated osteoblast differentiation in vitro. Therefore, contrary to what could be expected if osteoblasts contributed to spinal ankylosis, DHT inhibition might increase rather than decrease the progression of spinal ankylosis despite the higher levels of DHT observed in many AS patients.
تدمد: 1478-6362
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4552aba68b75b24005eb80ac016bfa0f
https://pubmed.ncbi.nlm.nih.gov/32448352
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....4552aba68b75b24005eb80ac016bfa0f
قاعدة البيانات: OpenAIRE
الوصف
تدمد:14786362