Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Cell Cycle. 2023 Jan;22(1):73-84. doi: 10.1080/15384101.2022.2109106. Epub 2022 Aug 7.
Emerging evidence indicated circadian clock gene Rev-erbα was involved in cartilage metabolism, however the contribution of Rev-erbα to growth plate chondrogenesis remains unknown. Here, we found that Rev-erbα exhibited the spatiotemporal expression model in growth plate. Moreover, Rev-erbα antagonist SR8278 inhibited longitudinal elongation of metatarsal bone ex vivo. And morphological analysis exhibited SR8278 led to the reduced height of growth plate and hypertrophic zone. Furthermore, blocking Rev-erbα suppressed the proliferation and hypertrophic differentiation of chondrocytes in growth plate. Similarly, knock-down Rev-erbα inhibited the proliferation and differentiation of primary chondrocytes in vitro. The mechanistic study indicated that knock-down Rev-erbα up-regulated MAPK-ERK1/2 pathway in chondrocytes. However, restraint of MAPK-ERK1/2 pathway alleviated partially SR8278-inhibited longitudinal elongation of metatarsal bone and growth plate development. Therefore, our results provide evidence of the vital role of Rev-erbα on growth plate chondrogenesis.
新兴证据表明，生物钟基因 Rev-erbα 参与软骨代谢，但其对生长板软骨发生的贡献尚不清楚。在这里，我们发现 Rev-erbα 在生长板中表现出时空表达模式。此外，Rev-erbα 拮抗剂 SR8278 抑制了跖骨干的体外纵向伸长。形态分析显示，SR8278 导致生长板和肥大区高度降低。此外，阻断 Rev-erbα 抑制了生长板中软骨细胞的增殖和肥大分化。同样，Rev-erbα 的敲低抑制了体外原代软骨细胞的增殖和分化。机制研究表明，Rev-erbα 的敲低在软骨细胞中上调了 MAPK-ERK1/2 通路。然而，MAPK-ERK1/2 通路的抑制部分缓解了 SR8278 抑制的跖骨干纵向伸长和生长板发育。因此，我们的结果为 Rev-erbα 在生长板软骨发生中的重要作用提供了证据。
