NGF-TrkA signaling by sensory nerves coordinates the vascularization and ossification of developing endochondral bone
| Autor: | Daniel L.J. Thorek, Labchan Rajbhandari, Brian C. Goh, Zhi Li, Feng Quan Zhou, Liliana Minichiello, Zhu Li, Ryan E. Tomlinson, Qian Zhang, Thomas M. Brushart, Arun Venkatesan, Thomas L. Clemens |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Sensory Receptor Cells sensory nerves Neovascularization Physiologic neurotrophic tyrosine kinase receptor type 1 Tropomyosin receptor kinase A General Biochemistry Genetics and Molecular Biology Receptor tyrosine kinase Article nerve growth factor 03 medical and health sciences Mice Osteogenesis Internal medicine medicine Animals Femur Progenitor cell Receptor trkA lcsh:QH301-705.5 Endochondral ossification endochondral bone biology Ossification Embryo Mammalian Hindlimb 030104 developmental biology Nerve growth factor Endocrinology lcsh:Biology (General) Animals Newborn nervous system biology.protein Signal transduction medicine.symptom Neurotrophin Signal Transduction |
| Zdroj: | Cell Reports, Vol 16, Iss 10, Pp 2723-2735 (2016) |
| Popis: | SummaryDeveloping tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA) directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkAF592A mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification. |
| Databáze: | OpenAIRE |
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