Fibroregulation of Mesenchymal Progenitor Cells by BMP-4 After Traumatic Muscle Injury
| Autor: | Youngmi Ji, Leon J. Nesti, Wesley M. Jackson, Matthew W. Kluk, Orna Amrani, Jun Onodera, Emily H. Shin |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Muscle tissue Bone Morphogenetic Protein 4 In Vitro Techniques Matrix (biology) Young Adult Blast Injuries Fibrosis medicine Humans Orthopedics and Sports Medicine Progenitor cell Muscle Skeletal Cartilage oligomeric matrix protein biology business.industry Mesenchymal stem cell Mesenchymal Stem Cells General Medicine medicine.disease Cell biology medicine.anatomical_structure Gene Expression Regulation Osteocalcin biology.protein Surgery Tumor necrosis factor alpha business |
| Zdroj: | Journal of Orthopaedic Trauma. 26:693-698 |
| ISSN: | 0890-5339 |
| Popis: | OBJECTIVES Traumatized muscle is a complex healing environment containing cells with robust reparative and regenerative potential interacting in a cytokine milieu that influences the function and differentiation of these cells, leading to a spectrum of healing responses. In particular, bone morphogenetic protein-4 (BMP-4) is of interest as a potential modulator of healing because its dysregulation has been associated with fibrosis and heterotopic ossification formation. We propose a descriptive study of altered BMP-4 expression in traumatized muscle tissue and to evaluate its role in the fibroregulatory function of resident mesenchymal progenitor cells (MPCs) at the protein- and gene-expression levels. METHODS Protein-level expression of BMP-4 from cells resident in traumatized muscle specimens was evaluated using ELISA and also using sodium dodecyl sulfate-polyacrylamide gel electrophoresis to compare BMP-4 in homogenized muscle tissue specimens. BMP-4, cartilage oligomeric matrix protein (COMP), and osteocalcin expression localization was analyzed via immunohistochemistry. Reverse transcription-polymerase chain reaction was performed to evaluate fibroregulatory gene expression in MPCs after treatment with BMP-4. RESULTS BMP-4 was present in all traumatized muscle tissue specimens. Immunohistochemistry demonstrated that traumatized muscle fibers contained greater number of cells expressing BMP-4 in a more disorganized fashion compared with control samples. Reverse transcription-polymerase chain reaction demonstrated that COMP, growth and differentiation factor-10, and integrin beta-2 were up-regulated, whereas tumor necrosis factor-alpha was significantly down-regulated. COMP expression was colocalized in the traumatized muscle tissue with osteocalcin. CONCLUSIONS BMP-4 has an effect on MPCs that seems to promote fibrotic tissue formation. These findings suggest that BMP-4, while promoting osteoinduction, may also act on MPCs to promote formation of a fibrotic osteoinductive matrix. Thus, this signaling axis might be a potential target for heterotopic ossification prevention. |
| Databáze: | OpenAIRE |
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