Department of Orthopedic, Luoyang Orthopedic Hospital of Henan Province, Luoyang, China.
Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
J Cell Mol Med. 2021 Nov;25(21):10175-10184. doi: 10.1111/jcmm.16954. Epub 2021 Oct 6.
Steroid-induced osteoblast apoptosis is a crucial pathological process in steroid-induced osteonecrosis of the femoral head (SONFH). Autophagy can resist apoptosis and AMPK plays an important role in autophagy regulation. Aucubin from the small tree Eucommia ulmoides Oliv., which has a long history of use in orthopaedics and traumatology in Asian medicine, can promote bone formation, but whether it can slow or prevent steroid-osteoblast apoptosis is unclear. Therefore, we investigated the pathogenesis of SONFH and how the osteoblast responds to aucubin under the dexamethasone stimulation. In human femoral head osteonecrosis specimens, we found that the autophage and apoptosis level were increased, and the AMPK signalling was crucial to autophagy. We observed that aucubin could prevent dexamethasone-induced apoptosis in osteoblasts by enhancing the level of autophagy. Further, we confirmed that the regulatory effect of aucubin on autophagy and apoptosis was achieved by activating AMPK signalling. We have demonstrated a mechanism of disease progression and shown that aucubin could enhance autophagy through AMPK signalling to prevent osteoblast apoptosis. These findings provide a basis for the further investigation of the potential therapeutic role of aucubin in the SONFH.
甾醇诱导的成骨细胞凋亡是甾醇诱导性股骨头坏死（SONFH）的一个关键病理过程。自噬可以抵抗细胞凋亡，而 AMPK 在自噬调节中发挥重要作用。从杜仲小乔木杜仲（Eucommia ulmoides Oliv.）中提取的桃叶珊瑚苷，在亚洲医学的骨科和创伤学中已有悠久的应用历史，可促进骨形成，但尚不清楚其是否能减缓或预防甾醇诱导的成骨细胞凋亡。因此，我们研究了 SONFH 的发病机制以及成骨细胞在地塞米松刺激下对桃叶珊瑚苷的反应。在人股骨头坏死标本中，我们发现自噬和凋亡水平增加，并且 AMPK 信号对自噬至关重要。我们观察到桃叶珊瑚苷通过增强自噬水平来预防地塞米松诱导的成骨细胞凋亡。此外，我们证实桃叶珊瑚苷通过激活 AMPK 信号对自噬和凋亡的调节作用。我们已经证明了疾病进展的机制，并表明桃叶珊瑚苷可以通过 AMPK 信号增强自噬来防止成骨细胞凋亡。这些发现为进一步研究桃叶珊瑚苷在 SONFH 中的潜在治疗作用提供了依据。
