Эпигенетическая регуляция ремоделирования костной ткани и ее роль в патогенезе первичного остеопороза

Раскрытие молекулярных механизмов развития первичного остеопороза имеет фундаментальное значение как с точки зрения понимания патогенеза заболеваний опорно-двигательного аппарата в целом, так и для выявления ключевых звеньев генетической и эпигенетической регуляции экспрессии генов ремоделирования костной ткани. Количество обнаруженных молекулярно-генетических маркеров остеопороза продолжает расти, однако существует очевидная необходимость описания их функциональных взаимодействий. Установлено, что такие взаимодействия сопряжены с контролем экспрессии ряда факторов транскрипции и дифференцировки мезенхимальных стволовых клеток по пути остеобластогенеза и адипогенеза, а моноцитарных предшественников – по пути остеокластогенеза. Кроме того, результаты эпигенетических исследований значительно расширили понимание роли посттрансляционных модификаций гистонов, ДНК-метилирования и РНК-интерференции как в молекулярном патогенезе первичного остеопороза, так и в регуляции развития костной ткани. Несмотря на это, знания не систематизированы и нуждаются в обобщении данных исследований роли эпигенетических модификаторов в развитии первичного остеопороза, и, что не менее важно, в описании влияния каждого известного эпигенетического механизма на отдельные молекулярные звенья процесса формирования и резорбции костной ткани в течение онтогенеза человека, в том числе у лиц пожилого возраста. Понимание того, какие молекулярно-генетические механизмы и регуляторные системы вовлечены в развитие данной нозологии, представляет потенциальный интерес для создания таргетной терапии, поскольку уже сейчас рассматривается вопрос о возможности применения микроРНК для узконаправленной регуляции генов. Кроме того, систематизация этих данных важна для изучения разницы массивов эпигенетических маркеров, в зависимости от расовой и этнической принадлежности. В представленной обзорной статье проанализированы соответствующие систематические обзоры и оригинальные статьи, собрана и классифицирована информация о современных достижениях в области изучения эпигенетических механизмов и их аберраций при первичном остеопорозе, а также рассмотрены результаты исследований эпигенетических механизмов на отдельных функциональных звеньях ремоделирования костной ткани.

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