ArticleBone research2020
Osteoblasts are inherently programmed to repel sensory innervation.
Article in Bone research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Sensing the skeleton: sensorineural regulation in bone.Nature reviews. Neuroscience · 2026Review
- [Bifunctional biomaterials: An innovative strategy for synergistic bone tumor therapy and bone regeneration].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Review
- PTH induced osteoblast Slit3 to decrease aberrant sensory innervation in degenerated vertebral endplates to relieve low back pain in mice.Bone research · 2026Article
- Axon guidance cue SLIT2 regulates the murine skeletal stem cell niche through sympathetic innervation.The Journal of clinical investigation · 2025Article
- Developments of Thermosensitive Hydrogel for Maxillofacial Bone Regeneration.Small science · 2025Review
- Deciphering cartilage neuro-immune interactions and innervation profile through 3D engineered osteoarthritic micropathophysiological system.Materials today. Bio · 2025Article
- Neuro-Immunomodulatory Potential of Nanoenabled 4D Bioprinted Microtissue for Cartilage Tissue Engineering.Advanced healthcare materials · 2025Article
- Wnt/β-catenin signaling pathway as an important mediator in muscle and bone crosstalk: A systematic review.Journal of orthopaedic translation · 2024Review
- Advancing Fingertip Regeneration: Outcomes from a New Conservative Treatment Protocol.Journal of clinical medicine · 2024Article
- Biomimetic bone-periosteum scaffold for spatiotemporal regulated innervated bone regeneration and therapy of osteosarcoma.Journal of nanobiotechnology · 2024Article
- Activation of CGRP receptor-mediated signaling promotes tendon-bone healing.Science advances · 2024Article
- Sema3A secreted by sensory nerve induces bone formation under mechanical loads.International journal of oral science · 2024Article
- Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone-Related Diseases: Intercellular Communication Messengers and Therapeutic Engineering Protagonists.International journal of nanomedicine · 2024Review
- Engineering a multicompartment in vitro model for dorsal root ganglia phenotypic assessment.Journal of biomedical materials research. Part B, Applied biomaterials · 2023Article
- The Impact of Tannic Acid Consumption on Bone Mineralization.Metabolites · 2023Review
- Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs.Frontiers in immunology · 2023Review
- Osteoclast-derived extracellular vesicles are implicated in sensory neurons sprouting through the activation of epidermal growth factor signaling.Cell & bioscience · 2022Article
- Mechanisms of bone pain: Progress in research from bench to bedside.Bone research · 2022Review
- Micropathological Chip Modeling the Neurovascular Unit Response to Inflammatory Bone Condition.Advanced healthcare materials · 2022Article
- Cutting-Edge Technologies for Inflamed Joints on Chip: How Close Are We?Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons. Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development. Yet, the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited. Here, we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth, evidenced under sensory neurons and osteoblastic-lineage cells crosstalk. The mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors expression. We identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A, Wnt4, and Shh expression culminating at late stage of OB differentiation. We noted a correlation between Shh expression profile, OB differentiation stages, and OB-mediated axonal repulsion. Blockade of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory axons. Finally, to strengthen our model, we localized the expression of Shh by osteoblasts in bone tissue. Overall, our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation, and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.