Abstract & Overview
Bone is a mineralized tissue that provides fundamental support for body posture and biomechanical forces. Bones have also been meticulously used by humans as fine tools for at least over 25,000 years, perpetually captivating our curiosity and driving exploration into its mysteries. In this perspective, we revisit the milestones in the history of bone biology since the 17th century, and highlighted the transformative impact of pioneering technologies. From macroanatomical observations to microscopic cellular analyses and molecular signaling pathway explorations, each milestone has heralded groundbreaking discoveries. These include the elucidation of Wollf’s Law, the regulatory mechanisms of calcium metabolism (via osteotropic parathyroid hormone analogs and calcitonin), as well as the revelation of critical cell interactions and signaling pathways in bone remodeling. These foundational insights deepen our understanding of bone as an enigmatic and underexplored tissue, but also yield significant clinical advancements. Bone biology stands poised for an explosive expansion of knowledge as we usher in the era of systems biology, propelled by cutting-edge multi-omics approaches, including single cell RNA sequencing (scRNA-seq) and spatial transcriptomics, as well as artificial intelligence. Therefore, challenges and future directions are discussed to navigate the complexities of integrating emerging technologies and to foster interdisciplinary collaborations that will propel bone biology research towards innovative breakthroughs and holistic solutions.