Following mechanical loading, osteoblasts may arise via activation, differentiation, or proliferation to form bone. Our objective was to ablate proliferating osteoblast lineage cells in order to investigate the importance of these cells as a source for loading‐induced bone formation. We utilized 3.6Col1a1‐tk mice in which replicating osteoblast lineage cells can be ablated in an inducible manner using ganciclovir (GCV). Male and female mice were aged to 5‐ and 12‐months and subjected to 5 days of tibial compression. “Experimental” mice were tk‐positive, treated with GCV; “control” mice were either tk‐negative treated with GCV, or tk‐positive treated with PBS. We confirmed that experimental mice had a decrease in tk‐positive cells that arose from proliferation. Next, we assessed bone formation after loading to low (7N) and high (11N) forces and observed that periosteal bone formation rate in experimental mice was reduced by approximately 70% for both forces. Remarkably, woven bone formation induced by high‐force loading was blocked in experimental mice. Loading‐induced lamellar bone formation was diminished but not prevented in experimental mice. We conclude that osteoblast proliferation induced by mechanical loading is a critical source of bone forming osteoblasts for maximal lamellar formation and is essential for woven bone formation.

中文翻译：

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增殖的成骨细胞是小鼠对负荷的最大骨合成代谢反应所必需的

机械负荷后，成骨细胞可能通过激活、分化或增殖而形成骨。我们的目标是消融增殖的成骨细胞谱系细胞，以研究这些细胞作为负荷诱导骨形成来源的重要性。我们使用了 3.6Col1a1-tk 小鼠，其中复制的成骨细胞谱系细胞可以使用更昔洛韦 (GCV) 以诱导方式消融。雄性和雌性小鼠分别为 5 个月和 12 个月大，并进行 5 天的胫骨压缩。“实验”小鼠是 tk 阳性，用 GCV 治疗；“对照”小鼠要么用 GCV 治疗 tk 阴性，要么用 PBS 治疗 tk 阳性。我们证实实验小鼠因增殖而减少了 tk 阳性细胞。下一个，我们评估了加载到低 (7N) 和高 (11N) 力后的骨形成，并观察到实验小鼠的骨膜骨形成率在两种力下均降低了约 70%。值得注意的是，在实验小鼠中，高负荷诱导的编织骨形成被阻断。在实验小鼠中，负荷诱导的层状骨形成减少但没有被阻止。我们得出结论，机械负荷诱导的成骨细胞增殖是最大板层形成的成骨成骨细胞的关键来源，并且对于编织骨形成至关重要。在实验小鼠中，负荷诱导的层状骨形成减少但没有被阻止。我们得出结论，机械负荷诱导的成骨细胞增殖是最大板层形成的成骨成骨细胞的关键来源，并且对于编织骨形成至关重要。在实验小鼠中，负荷诱导的层状骨形成减少但没有被阻止。我们得出结论，机械负荷诱导的成骨细胞增殖是最大板层形成的骨形成成骨细胞的关键来源，并且对于编织骨形成至关重要。