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Purpose <p>Despite numerous scientific literatures containing substantial research on bone tissue proteins, current investigations predominantly focus narrowly on deconstructing singular molecular mechanisms or characterizing individual protein functions within bone biological processes. This fragmented approach underscores the urgent need for integrative analyses that elucidate the complex interplay between critical biological processes and their proteomic effectors. Our study addresses this knowledge gap through a systematic review and functional characterization of core osteogenic biological processes, establishing critical connections between fundamental bone biology and protein engineering applications.</p> Methods <p>The key biological processes of the bone were discussed through Gene Ontology (GO). Proteins associated with each process were retrieved from the AmiGO database and subsequently analyzed using the STRING database and Cytoscape. Thereafter, proteins in the bone tissue were screened from the Human Protein Atlas (HPA) database using an Interactive Venn diagram.</p> Results <p>A total of 2429 bone development genes, 610 ossification genes, and 78 bone remodeling genes were systematically compiled, and their corresponding protein–protein interaction (PPI) networks were mapped and analyzed for each biological process. Then, 180 bone developmental protein genes, 191 ossification protein genes, and 50 bone remodeling genes were screened in 1592 bone tissue protein-coding genes. At last, 13 cocontained proteins of bone development, ossification, and bone remodeling in bone tissue were screened out.</p> Conclusion <p>Through systematic bioinformatics analysis, we have summarized and graphically represented visually displayed fundamental biological processes of the bone, their subordinate biological events, critical protein ensembles in HPA, and PPI networks. These findings can provide the rational design strategies for bone-regenerative materials by elucidating both the regeneration-essential proteins and their dynamic coordination during defect repair. This comprehensive framework not only maps core protein networks governing skeletal regeneration but also provides a blueprint for developing targeted biomaterial strategies that synergistically engage multiple biological components in bone repair mechanisms.</p> <p>Lay Summary.</p> <p>Skeletal pathologies represent a growing global health burden, compromising musculoskeletal integrity across diverse populations. Emerging as a revolutionary therapeutic paradigm, bone-regenerative engineering offers innovative solutions for critical bone defects and age-related bone diseases. Focusing on protein-mediated engineering solutions, our study established the first system-level screening platform integrating developmental, ossification, and remodeling pathways. By systematically identifying core proteins governing these interdependent processes, biomaterial engineers with a molecular blueprint are provided for developing smart regenerative scaffolds that coordinate multiple biological aspects of bone healing.</p> Graphical Abstract <p></p>

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Key Protein Design for Bone-Regenerative Engineering: From Core Biological Processes to Targeted Protein Discovery

  • 期刊论文

  • 发表日期：

    2025年6月2日

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  • Benjie Wei,
  • Ke Gao,
  • Yingxue Wang,
  • Baoyou Sun,
  • Zhichao Feng,
  • Congcong Zhang,
  • Chunhui Sun,
  • Hong Liu

摘要

Purpose

Despite numerous scientific literatures containing substantial research on bone tissue proteins, current investigations predominantly focus narrowly on deconstructing singular molecular mechanisms or characterizing individual protein functions within bone biological processes. This fragmented approach underscores the urgent need for integrative analyses that elucidate the complex interplay between critical biological processes and their proteomic effectors. Our study addresses this knowledge gap through a systematic review and functional characterization of core osteogenic biological processes, establishing critical connections between fundamental bone biology and protein engineering applications.

Methods

The key biological processes of the bone were discussed through Gene Ontology (GO). Proteins associated with each process were retrieved from the AmiGO database and subsequently analyzed using the STRING database and Cytoscape. Thereafter, proteins in the bone tissue were screened from the Human Protein Atlas (HPA) database using an Interactive Venn diagram.

Results

A total of 2429 bone development genes, 610 ossification genes, and 78 bone remodeling genes were systematically compiled, and their corresponding protein–protein interaction (PPI) networks were mapped and analyzed for each biological process. Then, 180 bone developmental protein genes, 191 ossification protein genes, and 50 bone remodeling genes were screened in 1592 bone tissue protein-coding genes. At last, 13 cocontained proteins of bone development, ossification, and bone remodeling in bone tissue were screened out.

Conclusion

Through systematic bioinformatics analysis, we have summarized and graphically represented visually displayed fundamental biological processes of the bone, their subordinate biological events, critical protein ensembles in HPA, and PPI networks. These findings can provide the rational design strategies for bone-regenerative materials by elucidating both the regeneration-essential proteins and their dynamic coordination during defect repair. This comprehensive framework not only maps core protein networks governing skeletal regeneration but also provides a blueprint for developing targeted biomaterial strategies that synergistically engage multiple biological components in bone repair mechanisms.

Lay Summary.

Skeletal pathologies represent a growing global health burden, compromising musculoskeletal integrity across diverse populations. Emerging as a revolutionary therapeutic paradigm, bone-regenerative engineering offers innovative solutions for critical bone defects and age-related bone diseases. Focusing on protein-mediated engineering solutions, our study established the first system-level screening platform integrating developmental, ossification, and remodeling pathways. By systematically identifying core proteins governing these interdependent processes, biomaterial engineers with a molecular blueprint are provided for developing smart regenerative scaffolds that coordinate multiple biological aspects of bone healing.

Graphical Abstract