rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2017-48-53rsp-2338Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHМолекулярные механизмы ингибирования активности расщепления коллагена деферриоксамином в хряще больных остеоартритомMOLECULAR MECHANISMS OF INHIBITION OF COLLAGEN CLEAVAGE ACTIVITY BY DEFEROXAMINE IN THE CARTILAGE OF PATIENTS WITH OSTEOARTHRITISЧетинаЕ. В.ChetinaE. V.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

etchetina@mail.ruМарковаГ. А.MarkovaG. A.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ЛогуновА. Л.LogunovA. L.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

КоломацкийВ. В.KolomatskyV. V.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

НарышкинЕ. А.NaryshkinE. A.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

МакаровС. А.MakarovS. A.

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

КузинА. Н.KuzinA. N.

115516 Москва, Тарный проезд, 3

3, Tarnyi Passage, Moscow 115516

ФГБНУ «Научно- исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationГБУЗ г. Москвы «Бюро судебно-медицинской экспертизы Департамента здравоохранения Москвы»РоссияBureau of Forensic and Medical ExaminationRussian Federation2017080320175514853Copyright © Четина Е.В., Маркова Г.А., Логунов А.Л., Коломацкий В.В., Нарышкин Е.А., Макаров С.А., Кузин А.Н., 20172017Четина Е.В., Маркова Г.А., Логунов А.Л., Коломацкий В.В., Нарышкин Е.А., Макаров С.А., Кузин А.Н.Chetina E.V., Markova G.A., Logunov A.L., Kolomatsky V.V., Naryshkin E.A., Makarov S.A., Kuzin A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2338

Цель – изучить молекулярные механизмы, обусловливающие подавление коллагеназной активности в присутствии деферриоксамина (ДФО) в эксплантатах суставного хряща больных остеоартритом (ОА).

Материал и методы

Материал и методы. Исследовали хрящ коленных суставов 33 больных ОА (средний возраст 61,6±10,3 года), полученный при эндопротезировании, и хрящ 25 человек, не страдавших ОА (средний возраст 40±6,1 года), полученный при аутопсии. Хрящ культивировали в присутствии 10 мкМ ДФО. Экспрессию генов в эксплантатах хряща определяли посредством обратно-транскриптазной и полимеразной цепной реакции в режимереального времени.

Результаты и обсуждение

Результаты и обсуждение. Снижение коллагеназной активности в присутствии ДФО в эксплантатах суставного хряща больных ОА, которое было нами показано ранее, сопровождалось значительным ингибированием экспрессии матриксных металлопротеиназ 13 и 1, а также катепсина К, обладающих коллагеназной активностью, а также маркера гипертрофии хондроцитов коллагена Х типа и провоспалительных цитокинов интерлейкина 1β и фактора некроза опухоли α. ДФО не изменял уровни экспрессии генов фосфоглицераткиназы и пируваткиназы, отвечающих за продукцию аденозинтрифосфата (АТФ) в гликолизе, а также транспортера глюкозы Glut 1. Напротив, экспрессия генов, связанных с генерацией АТФ в цикле трикарбоновых кислот: изоцитратдегидрогеназы, сукцинатдегидрогеназы, α-кетоглутаратдегидрогеназы и малатдегидрогеназы, а также аденозинмонофосфат-активируемой протеинкиназы (АМПК), значительно повышалась. Экспрессия АМПК в суставном хряще больных ОА была значительно ниже, чем у здоровых лиц.

Заключение

Заключение. Ингибирование расщепления коллагена в присутствии ДФО в эксплантатах суставного хряща больных ОА, которое сопровождалось значительным снижением экспрессии протеаз, ответственных за деструкцию внеклеточного матрикса, провоспалительных цитокинов и гипертрофии хондроцитов, обусловлено повышением активности митохондриального окислительного фосфорилирования в хондроцитах.

Objective

Objective: to study the molecular mechanisms underlying the suppression of collagenase activity in the presence of deferoxamine (DFO) in articular cartilage explants from patients with osteoarthritis (OA).

Subjects and methods

Subjects and methods. The knee joint cartilage obtained during arthroplasty from 33 patients (mean age, 61.8±10.3 years) with OA, and that derived at autopsy from 25 people (mean age 40±6.1 years) without this disease were investigated. The cartilage was cultured in the presence of 10 μm DFO. The gene expression in the cartilage explants was determined by real-time reverse transcriptase and polymerase chain reaction.

Results and discussion

Results and discussion. The reduced collagenase activity in the presence of DFO in the articular cartilage explants from patients with OA, which had been shown earlier, was accompanied by the significantly inhibited expression of matrix metalloproteinases 1 and 13 and cathepsin K, which had collagenase activity, as well as the marker of hypertrophic chondrocytes, such as X type collagen, and the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α. DFO did not change the expression levels of the phosphoglucomutase and pyruvate kinase genes responsible for the production of adenosine triphosphate (ATP) during glycolysis and the glucose transporter Glut 1. On the contrary, the expression of the genes associated with ATP generation in the tricarboxylic acid cycle: isocitrate dehydrogenase, succinate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase, and adenosine monophosphate- activated protein kinase (AMPK) significantly increased. The expression of AMPK in the articular cartilage of patients with OA was significantly lower than that in healthy individuals.

Conclusion

Conclusion. Inhibition of collagen cleavage in the presence of DFO in the articular cartilage explants from OA patients, which was accompanied by a considerable decrease in the expression of the proteases responsible for degradation of the extracellular matrix, proinflammatory cytokines and chondrocytes hypertrophy, was due to the enhanced activity of mitochondrial oxidative phosphorylation in the chondrocytes.

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The authors declare that there are no conflicts of interest present.