■糖皮质激素性股骨头坏死(GIONFH)是一种常见的骨关节疾病。目前缺乏有效的治疗GIONFH,并且疾病进展可能导致全髋关节置换术(THA)。GIONFH发病机制的确切机制仍未确定,新出现的证据表明,破骨细胞的过度活化在这种情况的发生和进展中起着关键作用。我们以前的研究表明,环黄芪醇(CAG),具有多种生物活性的三萜皂苷,是一种天然的破骨细胞抑制剂,对骨质流失有保护作用。然而,其对GIONFH的影响尚不清楚。
■在这项研究中,甲基强的松龙(MPS)(20mg/kg)通过臀肌注射给雌性Sprague-Dawley(SD)大鼠以诱导GIONFH,腹腔注射不同剂量的CAG(5和15mg/kg)进行干预。应用Micro-CT筛查和血管造影来确定坏死性病变的形态,骨小梁的丢失,以及当地血液供应的变化。通过实时qPCR和Western印迹建立了分子机制。进行苏木精和伊红(H&E)染色以鉴定股骨头中的空腔。
■CAG治疗缩短了坏死病变区域,抑制骨小梁丢失,改善股骨头局部供血。此外,CAG药物降低了Tnfsf11(编码RANKL)与Tnfrsf11b(编码OPG)的比例和破骨细胞特异性基因的表达,包括Acp5和Ctsk。始终如一,CAG治疗对破骨细胞生成和骨吸收相关蛋白的表达表现出剂量依赖性减弱作用,包括陷阱,CTSK,MMP9添加CAG还减轻了软骨下区域空腔隙的发生。
■我们的发现表明,CAG是GIONFH患者髋关节保留治疗的潜在选择。
■CAG对GIONFH大鼠的保护作用可转化为临床应用。
UNASSIGNED: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common bone and joint disease. There is currently a lack of effective treatment for GIONFH, and the disease progression may lead to total hip arthroplasty (THA). The exact mechanism of GIONFH pathogenesis remains unsettled, and emerging evidence indicates that the overactivation of osteoclasts plays a pivotal role in the occurrence and progression of this condition. Our previous
study has shown that cycloastragenol (CAG), a triterpenoid saponin with multiple bioactivities, is a natural
osteoclast inhibitor and has a protective effect on bone loss. However, its effect on GIONFH remains unclear.
UNASSIGNED: In this
study, methylprednisolone (MPS) (20 mg/kg) was administered via gluteal muscle injection to female Sprague-Dawley (SD) rats to induce GIONFH, and different doses of CAG (5 and 15 mg/kg) were dispensed intraperitoneally for intervention. Micro-CT screening and angiography were applied to determine the shaping of necrotic lesions, the loss of trabecular bone, and the change in the local blood supply. The molecular mechanism was established by Real-time qPCR and Western blotting. Hematoxylin and eosin (H&E) staining was performed to identify empty lacunae in the femoral head.
UNASSIGNED: CAG treatment shanked the necrotic lesion area, inhibited the trabecular bone loss, and improved the local blood supply in the femoral head. In addition, CAG medication lowered the ratio of Tnfsf11 (encoding RANKL) to Tnfrsf11b (encoding OPG) and the expression of
osteoclast-specific genes, including Acp5 and Ctsk. Consistently, CAG treatment exhibited a dose-dependent weakening effect on the expression of osteoclastogenesis and bone resorption-related proteins, including TRAP, CTSK, and MMP9. CAG addition also alleviated the occurrence of empty lacunae in the subchondral region.
UNASSIGNED: Our discoveries demonstrate that CAG is a potential option for hip preservation therapy in GIONFH patients.
UNASSIGNED: The protective effect of CAG on rats with GIONFH can be translated into clinical use.