Activation of JNK signaling in osteoblasts is inversely correlated with collagen synthesis in age-related osteoporosis
| Autor: | Yong-Jun Rui, Long Cheng, Ya Zhang, Jian Wang, Yapeng Wang, Xin Zhang, Minxuan Sun, Gang Zhao |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Collagen Type XII musculoskeletal diseases 0301 basic medicine MAP Kinase Signaling System Osteoporosis Biophysics Collagen Type VIII Protein Serine-Threonine Kinases MAP Kinase Kinase Kinase 4 Biochemistry Germinal Center Kinases Pathogenesis Transcriptome 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Humans Kinase activity Molecular Biology Gene Aged Osteoblasts Sequence Analysis RNA Chemistry Age Factors Cell Biology Middle Aged medicine.disease Cell biology 030104 developmental biology Gene Expression Regulation Immunohistochemistry Collagen Oxidoreductases 030217 neurology & neurosurgery Function (biology) |
| Zdroj: | Biochemical and Biophysical Research Communications. 504:771-776 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2018.08.094 |
| Popis: | The age-related reduction in the function of osteoblasts plays a central role in the pathogenesis of bone loss and osteoporosis. Collagen synthesis is a primary function of differentiated osteoblasts, however, the mechanisms for age-related changes in collagen synthesis in human osteoblasts remain elusive. We use Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) analysis to exploit the transcriptional profiles of osteoblasts from young and old donors. A panel of collagen members was downregulated in aged osteoblasts, including COL12A1, COL5A1, COL5A3, COL8A1 and COL8A2. Co-expression analysis followed by GO analysis revealed that oxidoreductase activity and kinase activity were inversely correlated with collagen synthesis in osteoblasts. GESA analysis further showed that JNK signaling was upregulated in aged osteoblasts. Consistently, MAP3K4 and MAP4K2, upstream of JNK, were also increased in aged osteoblasts. Moreover, expression levels of MAP3K4 were significantly inversely correlated with levels of the collagen genes. Those transcriptomic results were further verified by examining clinical specimens of osteoporosis by immunohistochemistry. These results provide transcriptomic evidence that deregulated JNK signaling may impair collagen synthesis in osteoblasts and imply a therapeutic value of JNK inhibitors for treating osteoporosis and preventing skeletal aging by counteracting the age-related reduction in the function of osteoblasts. |
| Databáze: | OpenAIRE |
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