Deep time evolution of bone cells and the implications for bone metabolism in vertebrate history

大多数脊椎动物都有细胞骨，其中骨细胞（骨细胞）被封闭在骨基质内的洞穴状腔隙中，并通过树突状细胞过程相互连接，这些树突状细胞过程延伸成一个高度复杂的小管网络（小管）。最近的研究表明，这种所谓的腔管网络在骨代谢中起着关键作用，如根据应变变化协调骨表面的建模和重塑，检测骨中的微裂缝并诱导其修复，并在矿物质平衡中发挥重要作用。此外，研究表明，每单位骨体积的骨细胞数量与骨生长速率成正比，其密度和形状取决于在形成过程中作用于某一骨骼的局部应变环境。鉴于现存脊椎动物骨代谢的多种功能，推测骨细胞分布和形态的模式可以为化石脊椎动物的生物学提供新的见解。然而，尽管骨腔管网络在骨化石中通常保存得很好，但骨细胞的进化史却鲜为人知。在拟议的项目中，将对整个脊椎动物历史中的腔隙管网络进行定量和定性研究，以获得对骨细胞进化的深入时间视角，从第一批具有细胞骨的脊椎动物，无颌骨动物，到基颌脊椎动物（placoderms和棘足动物），骨鱼鱼类，干四足动物，两栖动物和羊膜动物。化石骨将通过光学显微镜，扫描电子显微镜（SEM）和同步加速器x射线相衬断层扫描进行研究。重点在于腔隙的密度和排列，腔隙的形状和大小，小管的形态，以及嵌入腔隙系统的骨基质的类型。从化石分类群中获得的结果将与来自已知代谢率的现存脊椎动物的骨薄切片以及来自现代骨细胞生物学的数据进行比较。这将有助于推断代谢率、骨骼建模和重塑，以及对早已灭绝的动物骨骼起作用的局部应变机制，并将在体型、个体发生年龄和栖息地（例如水生与陆生）的背景下加以考虑。利用不同的指标对脊椎动物不同谱系的腔管特征进行系统发育信号的测试。这个项目的结果对于我们理解整个脊椎动物历史中骨代谢的发展，特别是在主要进化转变的背景下，将是重要的。

Most vertebrates have cellular bone in which bone cells (osteocytes) are enclosed in cave-like lacunae within the bone matrix and are connected to each other via dendritic cell processes that extend in a highly complex network of tubules (canaliculi). Recent studies have shown that this so called lacunocanalicular network plays a pivotal role in bone metabolism, like orchestrating modeling and reshaping of bone surfaces according to strain changes, detecting micro-cracks in bone and inducing their repair, and playing a significant role in mineral homoeostasis. Furthermore, it has been shown that the number of osteocytes per unit of bone volume is proportional to bone growth rate, and their density and shape varies depending on the local strain environment that acts on a certain bone during its formation. Given the multitude of functions in bone metabolism of extant vertebrates, it is inferred that patterns of osteocyte distribution and morphology allow new insights into the biology of fossil vertebrates. However, despite the fact that the lacunocanalicular network is usually well preserved in fossil bone, the evolutionary history of osteocytes is poorly known. In the proposed project, the lacunocanalicular network will be investigated quantitatively and qualitatively throughout vertebrate history to gain a deep time perspective on the evolution of osteocytes, spanning the range from the first vertebrates with cellular bone, the jawless osteostracans, to basal jawed vertebrates (placoderms and acanthodians), osteichthyan fishes, stem-tetrapods, amphibians, and amniotes. Fossil bone will be investigated by light microscopy, scanning electron microscopy (SEM), and synchrotron X-ray phase contrast tomography. The focus will lie on lacunar density and arrangement, lacunar shape and size, morphology of canaliculi, as well as the type of bone matrix in which the lacunocanalicular system is embedded. The results obtained from fossil taxa will be compared with osteological thin sections derived from extant vertebrates for which the metabolic rate is known, and with data from modern bone cell biology. This will allow to draw inferences about metabolic rate, bone modeling and remodeling, and local strain regimes that acted on the skeleton in long-extinct animals and will be regarded in the context of body size, ontogenetic age, and habitat (e.g., aquatic versus terrestrial). A test of phylogenetic signal of lacunocanalicular characters in different lineages of vertebrates will be conducted using different metrics. The results of this project will be important for our understanding of the development of bone metabolism throughout vertebrate history and especially against the background of major evolutionary transitions.