The bone extracellular matrix (ECM) contains minerals deposited on highly crosslinked collagen fibrils and hundreds of non-collagenous proteins. Some of these proteins are key to the regulation of bone formation and regeneration via signaling pathways, and play important regulatory and structural roles. However, the complete list of bone extracellular matrix proteins, their roles, and the extent of individual and cross-species variations have not been fully captured in both humans and model organisms. Here, we introduce the most comprehensive resource of bone extracellular matrix (ECM) proteins that can be used in research fields such as bone regeneration, osteoporosis, and mechanobiology. The Phylobone database (available at https://phylobone.com) includes 255 proteins potentially expressed in the bone extracellular matrix (ECM) of humans and 30 species of vertebrates. A bioinformatics pipeline was used to identify the evolutionary relationships of bone ECM proteins. The analysis facilitated the identification of potential model organisms to study the molecular mechanisms of bone regeneration. A network analysis showed high connectivity of bone ECM proteins. A total of 214 functional protein domains were identified, including collagen and the domains involved in bone formation and resorption. Information from public drug repositories was used to identify potential repurposing of existing drugs. The Phylobone database provides a platform to study bone regeneration and osteoporosis in light of (biological) evolution, and will substantially contribute to the identification of molecular mechanisms and drug targets.

骨细胞外基质 (ECM) 含有沉积在高度交联的胶原纤维和数百种非胶原蛋白上的矿物质。其中一些蛋白质是通过信号通路调节骨形成和再生的关键，并发挥重要的调节和结构作用。然而，人类和模型生物体中尚未完全掌握骨细胞外基质蛋白的完整列表、它们的作用以及个体和跨物种变异的程度。在这里，我们介绍最全面的骨细胞外基质（ECM）蛋白资源，可用于骨再生、骨质疏松和力学生物学等研究领域。Phylobone 数据库（可在 https://phylobone.com 获取）包括 255 种可能在人类和 30 种脊椎动物的骨细胞外基质 (ECM) 中表达的蛋白质。使用生物信息学流程来识别骨 ECM 蛋白的进化关系。该分析有助于识别潜在的模型生物体，以研究骨再生的分子机制。网络分析显示骨 ECM 蛋白具有高度连通性。总共鉴定出 214 个功能蛋白结构域，包括胶原蛋白和参与骨形成和吸收的结构域。来自公共药物存储库的信息被用来识别现有药物的潜在重新用途。Phylobone 数据库提供了一个根据（生物）进化研究骨再生和骨质疏松症的平台，并将大大有助于分子机制和药物靶点的识别。