1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites
| Autor: | Edmundo E. Carreon, Mohammad Safaie Yazdi, Xuezhong Qin, Kin-Hing William Lau, Charles H. Rundle, Samiksha Wasnik, Yi Xu, Xiaolei Tang, David J. Baylink |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Bone disease Priming (immunology) Oncostatin M Bone healing Bone and Bones Proinflammatory cytokine Mice 03 medical and health sciences Cell Movement Osteogenesis medicine Animals Humans Vitamin D Immunity Cellular Wound Healing biology Interleukin-6 Tumor Necrosis Factor-alpha Bone Injury Chemistry Macrophages Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells General Medicine medicine.disease RAW 264.7 Cells 030104 developmental biology Cancer research biology.protein Cytokines Research Article Adult stem cell |
| Zdroj: | JCI Insight. 3 |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.98773 |
| Popis: | An indispensable role of macrophages in bone repair has been well recognized. Previous data have demonstrated the copresence of M1 macrophages and mesenchymal stem cells (MSCs) during the proinflammatory stage of bone repair. However, the exact role of M1 macrophages in MSC function and bone repair is unknown. This study aimed to define the role of M1 macrophages at bone injury sites via the function of 1,25-Dihydroxyvitamin D (1,25[OH]2D) in suppressing M1 but promoting M2 differentiation. We showed that 1,25(OH)2D suppressed M1 macrophage–mediated enhancement of MSC migration. Additionally, 1,25(OH)2D inhibited M1 macrophage secretion of osteogenic proteins (i.e., Oncostatin M, TNF-α, and IL-6). Importantly, the 1,25(OH)2D-mediated suppression of osteogenic function in M1 macrophages at the proinflammatory stage was associated with 1,25(OH)2D-mediated reduction of MSC abundance, compromised osteogenic potential of MSCs, and impairment of fracture repair. Furthermore, outside the proinflammatory stage, 1,25(OH)2D treatment did not suppress fracture repair. Accordingly, our data support 2 conclusions: (a) M1 macrophages are important for the recruitment and osteogenic priming of MSCs and, hence, are necessary for fracture repair, and (b) under vitamin D–sufficient conditions, 1,25(OH)2D treatment is unnecessary and can be detrimental if provided during the proinflammatory stage of fracture healing. |
| Databáze: | OpenAIRE |
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