ArticlebioRxiv : the preprint server for biology2025
Multiscale 3D whole joint cellular and molecular mapping dissects the relationship between structure and pain.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Understanding musculoskeletal joints from a 3D multiscale perspective, from molecular to anatomical levels, is essential for resolving the confounding relationships between structure and pain, elucidating the intricate mechanisms regulating joint health and diseases, and developing new treatment strategies. Here, we introduce a musculoskeletal joint immunostaining and clearing (MUSIC) method specifically designed to overcome key challenges of immunostaining and optical clearing of intact joints. Coupled with large-field light sheet microscopy, our approach enables 3D high-resolution, microscale neurovascular mapping within the context of whole-joint anatomy without the need for image coregistration across various joints, including temporomandibular joints, knees, and spines, and multiple species, including mouse, rat, and pig. Our findings reveal 3D heterogeneous distributions of neurovascular networks and previously uncharacterized neurovascular pathways within joints. Using the proteoglycan 4 knockout (
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