Buss Daniel J, Deering Joseph, Reznikov Natalie, McKee Marc D
Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, School of Biomedical Sciences, McGill University, Montreal, QC H3A 0C7, Canada.
Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3A 0C7, Canada.
JBMR Plus. 2024 Dec 30;9(2):ziae176. doi: 10.1093/jbmrpl/ziae176. eCollection 2025 Feb.
Biomineralization in bones and teeth is a highly regulated extracellular event. In the skeleton, mineralization at the tissue level is controlled within the collagenous extracellular matrix by both circulating and local factors. While systemic regulation of mineral ion homeostasis has been well-studied over many decades, much less is known about the regulation of mineralization at the local level directly within the extracellular matrix. Some local regulators have been identified, such as tissue-nonspecific alkaline phosphatase (TNAP), phosphate-regulating endopeptidase homolog X-linked (PHEX), pyrophosphate, and osteopontin, and others are currently under investigation. Dysregulation of the actions of enzyme-inhibitor substrate pairs engaged in mineralization (as we describe by the for extracellular matrix mineralization) leads to osteomalacic "soft bone" diseases, such as hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH). This review addresses how advances in 3D imaging tools and software now allow contextual and correlative viewing and interpretation of mineralized tissue structure across most length scales. Contextualized and integrated 3D multiscale data obtained from these imaging modalities have afforded an unprecedented structural biology view of bone from the macroscale to the nanoscale. Such correlated volume imaging data is highly quantitative, providing not only an integrated view of the skeleton in health, but also a means to observe alterations that occur in disease. In the context of the many hierarchical levels of skeletal organization, here we summarize structural features of bone over multiple length scales, with a focus on nano- and microscale features as viewed by X-ray and electron tomography imaging methods (submicron μCT and FIB-SEM). We additionally summarize structural changes observed after dysregulation of the mineralization pathway, focusing here on the mouse model for XLH. More specifically, we summarize how mineral patterns/packs at the microscale (3D crossfibrillar mineral tessellation), and how this is defective in mouse bone and enthesis fibrocartilage.
骨骼和牙齿中的生物矿化是一个受到高度调控的细胞外过程。在骨骼中，组织水平的矿化在胶原细胞外基质内受到循环因子和局部因子的共同控制。虽然数十年来对矿质离子稳态的系统调节已得到充分研究，但对于细胞外基质内局部水平矿化的调节却知之甚少。一些局部调节因子已被确定，如组织非特异性碱性磷酸酶（TNAP）、X连锁磷酸盐调节内肽酶同源物（PHEX）、焦磷酸盐和骨桥蛋白，其他一些目前正在研究中。参与矿化的酶 - 抑制剂底物对的作用失调（正如我们所描述的细胞外基质矿化的 ）会导致骨软化性“软骨”疾病，如低磷血症（HPP）和X连锁低磷血症（XLH）。本综述探讨了3D成像工具和软件的进展如何使我们能够在大多数长度尺度上对矿化组织结构进行背景关联观察和解读。从这些成像方式获得的背景化和整合的3D多尺度数据提供了从宏观到纳米尺度前所未有的骨骼结构生物学视角。这种相关的体积成像数据具有高度定量性，不仅提供了健康状态下骨骼的整体视图，还提供了观察疾病中发生变化的手段。在骨骼组织的多个层次背景下，我们在此总结了多个长度尺度上骨骼的结构特征，重点关注通过X射线和电子断层扫描成像方法（亚微米μCT和FIB - SEM）观察到的纳米和微米尺度特征。我们还总结了矿化途径失调后观察到的结构变化，这里重点关注XLH的 小鼠模型。更具体地说，我们总结了微观尺度（3D跨纤维矿化镶嵌）的矿化模式/堆积情况，以及在 小鼠骨骼和 韧带纤维软骨中这种情况是如何存在缺陷的。
