Andersen Thomas Levin, Sondergaard Teis Esben, Skorzynska Katarzyna Ewa, Dagnaes-Hansen Frederik, Plesner Trine Lindhardt, Hauge Ellen Margrethe, Plesner Torben, Delaisse Jean-Marie
Department of Clinical Cell Biology, Vejle Hospital, Institute of Regional Health Services Research (IRS-CSFU), University of Southern Denmark, Vejle, Denmark.
Am J Pathol. 2009 Jan;174(1):239-47. doi: 10.2353/ajpath.2009.080627. Epub 2008 Dec 18.
During skeletal remodeling, pre-osteoclasts and pre-osteoblasts are targeted to critical sites of the bone to resorb and reconstruct bone matrix, respectively. Coordination of site-specific recruitment of these two cell types is a prerequisite to maintain the specific architecture of each bone within strict limits throughout adult life. Here, we determined that the bone marrow microanatomy adjacent to remodeling areas is a central player in this process. By using histomorphometry and multiple immunostainings, we demonstrated in biopsies exhibiting coupled bone resorption and formation that osteoclasts and osteoblasts on the bone surface were always covered by a canopy of flat cells expressing osteoblast markers. In contrast, in biopsies in which this canopy was disrupted, bone formation was deficient. Three-dimensional visualizations revealed that this canopy covered the entire remodeling site and was associated with capillaries, thereby forming a previously unrecognized microanatomical entity. Furthermore, pre-osteoclasts were positioned along these capillaries. These findings led to a model that implicates vasculature in the site-specific recruitment of osteoclasts and osteoblasts and embraces the current knowledge on the molecular mechanism of bone remodeling.
在骨骼重塑过程中，破骨前体细胞和成骨前体细胞分别被定向到骨骼的关键部位，以吸收和重建骨基质。在成年期，协调这两种细胞类型的位点特异性募集是在严格限制内维持每块骨骼特定结构的前提条件。在此，我们确定与重塑区域相邻的骨髓微解剖结构是这一过程的核心参与者。通过组织形态计量学和多重免疫染色，我们在显示耦合性骨吸收和形成的活检样本中证明，骨表面的破骨细胞和成骨细胞总是被一层表达成骨细胞标志物的扁平细胞所覆盖。相比之下，在这层覆盖物被破坏的活检样本中，骨形成不足。三维可视化显示，这层覆盖物覆盖了整个重塑部位，并与毛细血管相关联，从而形成了一个以前未被认识的微解剖实体。此外，破骨前体细胞沿着这些毛细血管排列。这些发现得出了一个模型，该模型表明脉管系统参与破骨细胞和成骨细胞的位点特异性募集，并包含了目前关于骨重塑分子机制的知识。
