Etidronate (HEBP) promotes osteoblast differentiation and wound closure in rat calvaria
Etidronate (HEBP) promotes osteoblast differentiation and wound closure in rat calvaria
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DOI：
10.1007/s004419900165
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发表时间：
2000-12-01
影响因子：
3.6
通讯作者：
Lekic, PC
中科院分区：
文献类型：
--
作者：
D'Aoust, P;McCulloch, CAG;Lekic, PC
调控体内成骨细胞群迁移、增殖和分化的机制尚不清楚。阐明这些机制对于理解决定矿化结缔组织稳态和再生的基本过程至关重要。已知双膦酸盐调节骨代谢，部分通过影响破骨细胞吸收。鉴于其他体外和体内研究的先前数据，我们认为它们也可能影响体内成骨细胞的增殖和分化。我们使用双膦酸盐（乙烷-1-羟基-1,1-双膦酸盐，HEBP，地替膦酸盐）和颅骨伤口模型来验证这一假设，在颅骨伤口模型中，成骨分化和骨形成是由损伤刺激协调诱导的。在20只雄性Wistar大鼠的颅骨上制造了伤口。术后每天用HEBP或生理盐水（对照组）治疗1或2周，每组5只大鼠术后1或2周处死。细胞增殖和克隆生长在死亡前1小时用h -3胸腺嘧啶标记，然后放射自显影。骨桥蛋白和骨唾液蛋白免疫组化染色测定成骨细胞群的细胞分化情况。Von Kossa染色和甲苯胺蓝染色用于评估矿化和类骨形成，并用于伤口愈合的形态计量学分析。术后1周和2周，HEBP促进伤口愈合(>比对照组高2倍，p50比生理盐水对照组高50%，p50比伤口附近的骨桥蛋白细胞内染色增加(p50比对照组高，P
The mechanisms that regulate the migration, proliferation and differentiation of osteogenic cell populations in vivo are poorly understood. Elucidation of these mechanisms is essential for an understanding of the basic processes that determine mineralized connective tissue homeostasis and regeneration. Bisphosphonates are known to regulate bone metabolism, in part through effects on osteoclastic resorption. Given previous data from other in vitro and in vivo investigations, we considered that they could also affect the proliferation and differentiation of osteoblasts in vivo. We tested this hypothesis using a bisphosphonate (ethane-1-hydrdxy-1,1-bisphosphonate, HEBP, etidronate) and a calvarial wound model in which osteogenic differentiation and bone formation are coordinately induced by the wounding stimulus. Wounds through the calvarial bone were created in 20 male Wistar rats. After surgery, animals were treated every day for 1 or 2 weeks with HEBP or saline (controls) and five rats in each group were killed at 1 or 2 weeks following surgery. Cellular proliferation and clonal growth were assessed by H-3-thymidine labeling 1 h before death followed by radioautography. Cellular differentiation of osteogenic cell populations was determined by immunohistochemical staining for osteopontin and bone sialoprotein. Von Kossa and toluidine blue staining were used for the assessment of mineralization and osteoid formation, and for morphometric analysis of wound closure. At 1 and 2 weeks after surgery HEBP promoted wound closure (>twofold greater than controls, P50% higher than saline controls, P50% increase in intracellular staining for osteopontin in the endosteum-lined spaces adjacent to the wound (P50% greater than controls, P