School/Hospital of Stomatology, Guizhou Medical University, Guizhou 550004, P.R. China.
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Exp Biol Med (Maywood). 2021 Aug;246(15):1727-1739. doi: 10.1177/15353702211011052. Epub 2021 Apr 29.
Bone mass loss (osteoporosis) seen in postmenopausal women is an adverse factor for implant denture. Using an ovariectomized rat model, we studied the mechanism of estrogen-deficiency-caused bone loss and the therapeutic effect of Zoledronic acid. We observed that ovariectomized-caused resorption of bone tissue in the mandible was evident at four weeks and had not fully recovered by 12 weeks post-ovariectomized compared with the sham-operated controls. Further evaluation with a TUNEL assay showed ovariectomized enhanced apoptosis of osteoblasts but inhibited apoptosis of osteoclasts in the mandible. Zoledronic acid given subcutaneously as a single low dose was shown to counteract both of these ovariectomized effects. Immunohistochemical staining showed that ovariectomized induced the protein levels of RANKL and the 65-kD subunit of the NF-κB complex mainly in osteoclasts, as confirmed by staining for TRAP, a marker for osteoclasts, whereas zoledronic acid inhibited these inductions. Western blotting showed that the levels of RANKL, p65, as well as the phosphorylated form of p65, and IκB-α were all higher in the ovariectomized group than in the sham and ovariectomized + zoledronic acid groups at both the 4th- and 12th-week time points in the mandible. These data collectively suggest that ovariectomized causes bone mass loss by enhancing apoptosis of osteoblasts and inhibiting apoptosis of osteoclasts. In osteoclasts, these cellular effects may be achieved by activating RANKL-NF-κB signalling. Moreover, zoledronic acid elicits its therapeutic effects in the mandible by counteracting these cellular and molecular consequences of ovariectomized.
绝经后女性的骨量流失（骨质疏松症）是影响种植义齿的不利因素。我们利用去卵巢大鼠模型研究了雌激素缺乏导致骨丢失的机制以及唑来膦酸的治疗作用。我们观察到，去卵巢导致下颌骨骨组织的吸收在四周时明显，并在去卵巢后 12 周时仍未完全恢复，与假手术对照组相比。进一步用 TUNEL 检测评估发现，去卵巢增强了下颌骨成骨细胞的凋亡，但抑制了破骨细胞的凋亡。单次皮下给予低剂量唑来膦酸可拮抗这两种去卵巢作用。免疫组织化学染色显示，去卵巢诱导 RANKL 蛋白水平和 NF-κB 复合物的 65-kD 亚基主要在上皮细胞中，这一点通过对破骨细胞标志物 TRAP 的染色得到证实，而唑来膦酸抑制了这些诱导作用。Western blot 显示，RANKL、p65 以及磷酸化形式的 p65 和 IκB-α 的水平在去卵巢组中均高于假手术组和去卵巢+唑来膦酸组，在第 4 周和第 12 周时在下颌骨中。这些数据共同表明，去卵巢通过增强成骨细胞的凋亡和抑制破骨细胞的凋亡导致骨量流失。在上皮细胞中，这些细胞效应可能通过激活 RANKL-NF-κB 信号通路来实现。此外，唑来膦酸通过拮抗去卵巢的这些细胞和分子后果，在颌骨中发挥其治疗作用。
