去卵巢小鼠股骨干合成代谢作用的组织化学评价

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Biosciences Pub Date : 2025-04-18 DOI:10.1016/j.job.2025.100663

Xuanyu Liu , Tomoka Hasegawa , Mako Sakakibara , Tomomaya Yamamoto , Mai Haraguchi-Kitakamae , Hotaka Ishizu , Yan Shi , Jiaxin Cui , Weisong Li , Wang Haoyu , Hiromi Hongo , Tomohiro Shimizu , Yoichi Ohiro , Norio Amizuka

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引用次数: 0

摘要

目的通过对去卵巢小鼠的股骨进行组织化学检测，探讨甲状旁腺激素相关肽类似物阿巴巴拉肽诱导骨合成代谢的机制。方法12周龄雌性C57BL/6J小鼠经卵巢切除术（OVX）后，每天腹腔注射阿巴巴拉肽（30 μg/kg/d: OVX + ABL组）或对照物（OVX组）。在给药后0、2、4和6周采集股骨，进行显微ct成像、TRAP、组织蛋白酶K、ALP和PHOSPHO1染色，并进行钙黄蛋白标记。结果OVX组骨小梁数和骨体积随时间逐渐减少，而OVX + ABL组在OVX后6周内保持不变。在OVX和OVX + ABL组之间，每个骨表面积的trap阳性/cathepsin k反应性破骨细胞的数量相似，除了OVX组在4周时暂时增加。OVX组中，alp阳性的成骨细胞和phospho1反应的成熟成骨细胞的面积减少，而OVX + ABL组中，alp阳性的成骨细胞包围小梁，并且长列的phospho1反应的成熟成骨细胞扩展到小梁末端区域。此外，在略凸的新骨上可见长时间连续的钙黄蛋白标记，表明OVX + ABL组骨形成基于建模。OVX + ABL组骨形成率/骨面比和基于模型的骨形成位点总长度均高于OVX组。结论阿巴帕肽通过促进骨重建和骨模型形成来抑制卵巢切除术后骨丢失。

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Histochemical assessment of the anabolic effects of abaloparatide on the femoral metaphyses of ovariectomized mice

Objective

To clarify the mechanism of bone anabolism induced by the parathyroid hormone-related peptide analog abaloparatide, we histochemically examined the femora of ovariectomized mice treated with abaloparatide.

Methods

Twelve-week-old female C57BL/6J mice underwent ovariectomies (OVX), and were then administered either abaloparatide (30 μg/kg/day: OVX + ABL group) or vehicle (OVX group) via daily intraperitoneal injection. Femora were harvested at 0, 2, 4, and 6 weeks post-administration and subjected to micro-CT imaging, TRAP, cathepsin K, ALP, and PHOSPHO1 staining, along with calcein labeling.

Results

In the OVX group, trabecular number and bone volume gradually decreased over time, whereas the OVX + ABL group maintained these values to 6 weeks after OVX. The numbers of TRAP-positive/cathepsin K-reactive osteoclasts per bone surface area were similar between the OVX and OVX + ABL group, except for a temporary increase at 4 weeks in the OVX group. In the OVX group, the areas of ALP-positive osteoblastic cells and PHOSPHO1-reactive mature osteoblasts decreased, whereas in the OVX + ABL group, ALP-positive osteoblastic cells surrounded the trabeculae, and long lines of PHOSPHO1-reactive mature osteoblasts expanded to the terminal region of the trabeculae. In addition, long continuous calcein labeling was seen on slightly convex new bone, indicating modeling-based bone formation in the OVX + ABL group. The bone formation rate/bone surface ratio and the total length of modeling-based bone formation sites were higher in the OVX + ABL group than in the OVX group.