Department of Oral Anatomy and Developmental Biology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Department of Oral Anatomy and Developmental Biology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Injury. 2021 Jun;52(6):1300-1309. doi: 10.1016/j.injury.2021.02.020. Epub 2021 Feb 14.
The fracture repair process is known to be delayed in postmenopausal women, under estrogen-deficient status. Osteoporotic fracture mainly occurs in the metaphyseal region of the long bone; however, most studies on fracture healing have focused on the diaphyseal region. In this study, we compared the repair process between metaphysis and diaphysis of ovariectomized (OVX) and Sham mice, and analyzed the effects of short-term estrogen administration in OVX mice. Mice were divided into four experimental groups, including Sham, OVX, OVX + vehicle, and OVX + 17β-estradiol (E2). Bone apertures were formed in the tibial metaphysis and diaphysis. The samples were collected and examined by micro-computed tomography, and using histological, histochemical, and immunohistochemical analysis at different time points after the surgery. The cartilaginous callus was formed at the diaphysis site of both the groups, which was sequentially replaced by bone on the periosteum side. Medullary callus was formed in all the groups; however, the volume of the callus in OVX mice was significantly lesser (˜30%) than that in Sham mice. Furthermore, in the metaphysis, no differences were observed in the medullary callus and bone mineral density between the two groups from day 21 to 28. The diaphysis of OVX group was not completely repaired even by day 28. In both the sites of OVX mice, ALP activity and disappearance of Gr-1 positive cells were delayed compared to that of Sham. Estrogen administration improved medullary callus formation in the diaphysis, however not in the metaphysis. The effect of ovariectomy on the repair process in diaphysis was greater than that in metaphysis. Our findings clarify the differences between the metaphysis and diaphysis repair process using OVX mouse model and suggest that the estrogen sensitivities differ between the sites during the bone repair process.
骨折修复过程已知在雌激素缺乏的绝经后妇女中延迟。骨质疏松性骨折主要发生在长骨的骨干骺端区域；然而，大多数骨折愈合研究都集中在骨干区域。在这项研究中，我们比较了去卵巢（OVX）和假手术（Sham）小鼠骺板和骨干的修复过程，并分析了短期雌激素给药对 OVX 小鼠的影响。将小鼠分为四组实验，包括 Sham、OVX、OVX+vehicle 和 OVX+17β-雌二醇（E2）。在胫骨骺板和骨干形成骨开口。在手术后不同时间点通过微计算机断层扫描和组织学、组织化学和免疫组织化学分析收集和检查样本。两组的骨干部位均形成软骨性骨痂，随后在骨膜侧被骨取代。所有组均形成髓腔骨痂；然而，OVX 小鼠的骨痂体积明显较小（约 30%）。此外，在 21 至 28 天期间，两组之间骺板的髓腔骨痂和骨密度没有差异。即使在第 28 天，OVX 组的骨干也未完全修复。在 OVX 小鼠的两个部位，碱性磷酸酶（ALP）活性和 Gr-1 阳性细胞的消失均延迟。雌激素给药改善了骨干的髓腔骨痂形成，但对骺板没有作用。去卵巢对骨干修复过程的影响大于骺板。我们的研究结果阐明了使用 OVX 小鼠模型的骺板和骨干修复过程之间的差异，并表明在骨修复过程中，雌激素敏感性在不同部位存在差异。
