Substance P signaling mediates BMP-dependent heterotopic ossification
| Autor: | Eileen M. Shore, Stuart R. Stock, John A. Kessler, Norma P. Gerard, Frederick S. Kaplan, Tammy L. McGuire, Yijie Liu, Lixin Kan, Vitali Y. Lounev, Lishu Duan, Bao Lu, Robert J. Pignolo |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Sensory Receptor Cells Mice Transgenic Inflammation Substance P Bone Morphogenetic Protein 4 Isoindoles Bone morphogenetic protein Biochemistry Article Mice chemistry.chemical_compound Neurokinin-1 Receptor Antagonists Tachykinins Internal medicine medicine Animals Humans Protein Precursors Molecular Biology Ossification Chemistry Ossification Heterotopic Cell Biology Myositis ossificans Receptors Neurokinin-1 medicine.disease Immunohistochemistry Endocrinology Myositis Ossificans Bone morphogenetic protein 4 Fibrodysplasia ossificans progressiva Bone Morphogenetic Proteins Cancer research Female Heterotopic ossification medicine.symptom |
| Zdroj: | Journal of Cellular Biochemistry. 112:2759-2772 |
| ISSN: | 0730-2312 |
| Popis: | Heterotopic ossification (HO) is a disabling condition associated with neurologic injury, inflammation, and overactive bone morphogenetic protein (BMP) signaling. The inductive factors involved in lesion formation are unknown. We found that the expression of the neuro-inflammatory factor Substance P (SP) is dramatically increased in early lesional tissue in patients who have either fibrodysplasia ossificans progressiva (FOP) or acquired HO, and in three independent mouse models of HO. In Nse-BMP4, a mouse model of HO, robust HO forms in response to tissue injury; however, null mutations of the preprotachykinin (PPT) gene encoding SP prevent HO. Importantly, ablation of SP(+) sensory neurons, treatment with an antagonist of SP receptor NK1r, deletion of NK1r gene, or genetic down-regulation of NK1r-expressing mast cells also profoundly inhibit injury-induced HO. These observations establish a potent neuro-inflammatory induction and amplification circuit for BMP-dependent HO lesion formation, and identify novel molecular targets for prevention of HO. |
| Databáze: | OpenAIRE |
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