porozendoОстеопороз и остеопатииOsteoporosis and Bone Diseases2072-26802311-0716Endocrinology Research Centre10.14341/osteo2015128-37porozendo-8902Research ArticleСтатьиArticlesЭНДОКРИННАЯ ФУНКЦИЯ КОСТНОЙ ТКАНИTHE ENDOCRINE FUNCTION OF THE BONE TISSUEГребенниковаТ АGrebennikovaT A

ординатор отделения нейроэндокринологии и остеопатий

-БелаяЖ ЕBelayaZh E

главный научный сотр. отделения нейроэндокринологии и остеопатий, д.м.н.

-ЦориевТ ТTsorievT T

ординатор отделения нейроэндокринологии и остеопатий

-РожинскаяЛ ЯRozhinskayaL Ya

зав. отделением нейроэндокринологии и остеопатий, д.м.н., профессор

rozhinskaya@rambler.ruМельниченкоГ АMelnichenkoG A

зам. директора , д.м.н., профессор, академик РАН

-ФГБУ Эндокринологический научный центр МЗ РФ201515122015181№1 (2015)2837Copyright © Гребенникова Т.А., Белая Ж.Е., Цориев Т.Т., Рожинская Л.Я., Мельниченко Г.А., 20152015Гребенникова Т.А., Белая Ж.Е., Цориев Т.Т., Рожинская Л.Я., Мельниченко Г.А.Grebennikova T.A., Belaya Z.E., Tsoriev T.T., Rozhinskaya L.Y., Melnichenko G.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.osteo-endojournals.ru/jour/article/view/8902

Обзор литературы посвящен обсуждению биологической функции гормонов, продуцируемых скелетом: фактора роста фибробластов 23 (ФРФ23) и остеокальцина. ФРФ23 секретируется остеоцитом и воздействует на почки, ингибируя 1-альфа-гидроксилазу, что предупреждает активацию витамина D, а также способствует выведению фосфора через почечные канальцы. Сродство ФРФ23 к рецептору фактора роста фибробластов (ФРФ-Р) низкое, однако при взаимодействии ФРФ23 и Клото связь значительно повышается и происходит активация рецепторного комплекса. Таким образом, Клото определяет преимущественно почечные эффекты ФРФ23. Увеличение содержания ФРФ23 или Клото из-за генетических нарушений или эктопической продукции опухолью сопряжено со снижением уровня фосфора в сыворотке крови человека. Напротив, низкое содержание ФРФ23 или Клото приводит к гиперфосфатемии и эктопической кальцификации. Генетические исследования на моделях мышей показали, что продукт секреции остеобластов - остеокальцин, в декарбоксилированной форме оказывает воздействие на ß-клетки поджелудочной железы, увеличивая продукцию инсулина, а в периферических тканях его эффекты повышают утилизацию глюкозы в результате повышения чувствительности к инсулину и уменьшают содержание висцерального жира. Кроме того, декарбоксилированный остеокальцин может оказывать прямые гормональные эффекты на клетки Лейдига у мужчин, усиливая секрецию тестостерона, что было показано в исследованиях, как на культурах клеток, так и у живых особей. В обоих случаях, при эффектах на поджелудочную железу и на яички, остеокальцин оказывает воздействие через GPCR6A рецептор, в результате активации которого запускается цАМФ связанный сигнальный путь. Таким образом, статья обобщает исследования, посвященные эндокринной функции костной ткани. гуморальные факторы, такие как секретируемый белок связанный с фризельдом 4 (SRFP4), матричный внеклеточный фосфогликопротеин (MEPE), фактор роста фибробластов 7 (ФРФ7), которые также способствуют развитию гипофосфатемии [4]. В настоящее время биологическая роль ФРФ23 активно изучается в связи с его влиянием на метаболизм фосфатов при хронической болезни почек (ХБП) и развитие вторичного гиперпаратиреоза. ФРФ23 рассматривается как возможный предиктор развития минерально-костных осложнений ХБП на доклинической стадии для ранней коррекции нарушений и замедления их прогрессирования. Возможно, ФРФ23 и его ко-рецептор Клото вовлечены в механизмы развития атеросклероза у пациентов с почечной недостаточностью. Соответственно изучаются перспективы фармакологического влияния на ФРФ23, которое может открыть новые перспективы в лечении осложнений ХБП [5,6]. Проводятся исследования влияния ФРФ23 на процессы, не связанные с фосфорно-кальциевым обменом, так, на данный момент, известно об участии гормона в развитии гипертрофии левого желудочка [7].

This review discusses the recent evidence showing that the skeleton itself produces at least two hormones: fibroblast growth factor 23 (FGF23) and osteocalcin. FGF23 is secreted by osteocytes in bone and acts on the kidney to inhibit 1-alpha-hydroxilation ofvitamin D and promote phosphorous excretion. The affinity of FGF23 to FGF receptor is low, but FGF23 binds to FGF receptor-Klotho complex with more affinity. Therefore, Klotho determines the kidney-specific action of FGF23. Increase in FGF23 or Klotho levels due to genetic defects or ectopic production results in low serum phosphorous levels in humans. Contrary to this, low FGF23 or Klotho levels lead to hypophosphatemia and ectopic calcification. Mouse genetics studies revealed that osteoblast product, osteocalcin, in its undercarboxylated stage acts on the pancreatic beta-cells to enhance insulin production and on peripheral tissues to increase glucose utilization as a result of increased insulin sensitivity and to reduce visceral fat. In addition to this, undercarboxylated osteocalcin may also have another hormonal role, this time as a mediator of testosterone secretion. Osteocalcin was shown to induce testosterone production in Leydig cells of the testes both in ex vivo and in vivo studies. In both localizations, at the pancreas and at the testes osteocalcin acts through the GPCR6A receptor, this activates the cAMP response element-binding protein signaling pathway. Thus, this review reports the recent studies indicating bone ’s role as an endocrine organ.

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