IL-17RA Signaling in Prx1+ Mesenchymal Cells Influences Fracture Healing in Mice
Fracture healing is a complex series of events that requires a local inflammatory reaction to initiate the reparative process. This inflammatory reaction is important for stimulating the migration and proliferation of mesenchymal progenitor cells from the periosteum and surrounding tissues to form t...
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/3751 |
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| author | Joseph L. Roberts David Kapfhamer Varsha Devarapalli Hicham Drissi |
| author_facet | Joseph L. Roberts David Kapfhamer Varsha Devarapalli Hicham Drissi |
| author_sort | Joseph L. Roberts |
| collection | DOAJ |
| description | Fracture healing is a complex series of events that requires a local inflammatory reaction to initiate the reparative process. This inflammatory reaction is important for stimulating the migration and proliferation of mesenchymal progenitor cells from the periosteum and surrounding tissues to form the cartilaginous and bony calluses. The proinflammatory cytokine interleukin (IL)-17 family has gained attention for its potential regenerative effects; however, the requirement of IL-17 signaling within mesenchymal progenitor cells for normal secondary fracture healing remains unknown. The conditional knockout of IL-17 receptor a (<i>Il17ra</i>) in mesenchymal progenitor cells was achieved by crossing <i>Il17ra</i><sup>F/F</sup> mice with <i>Prx1-cre</i> mice to generate <i>Prx1-cre</i>; <i>Il17ra</i><sup>F/F</sup> mice. At 3 months of age, mice underwent experimental unilateral mid-diaphyseal femoral fractures and healing was assessed by micro-computed tomography (µCT) and histomorphometric analyses. The effects of IL-17RA signaling on the osteogenic differentiation of fracture-activated periosteal cells was investigated in vitro. Examination of the intact skeleton revealed that the conditional knockout of <i>Il17ra</i> decreased the femoral cortical porosity but did not affect any femoral trabecular microarchitectural indices. After unilateral femoral fractures, <i>Il17ra</i> conditional knockout impacted the cartilage and bone composition of the fracture callus that was most evident early in the healing process (day 7 and 14 post-fracture). Furthermore, the in vitro treatment of fracture-activated periosteal cells with IL-17A inhibited osteogenesis. This study suggests that IL-17RA signaling within <i>Prx1</i>+ mesenchymal progenitor cells can influence the early stages of endochondral ossification during fracture healing. |
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| language | English |
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| publishDate | 2024-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7123fe7cc97740f99fdc0737ce94b9702024-04-12T13:19:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01257375110.3390/ijms25073751IL-17RA Signaling in Prx1+ Mesenchymal Cells Influences Fracture Healing in MiceJoseph L. Roberts0David Kapfhamer1Varsha Devarapalli2Hicham Drissi3Department of Orthopaedics, Emory University, Atlanta, GA 30329, USADepartment of Orthopaedics, Emory University, Atlanta, GA 30329, USADepartment of Orthopaedics, Emory University, Atlanta, GA 30329, USADepartment of Orthopaedics, Emory University, Atlanta, GA 30329, USAFracture healing is a complex series of events that requires a local inflammatory reaction to initiate the reparative process. This inflammatory reaction is important for stimulating the migration and proliferation of mesenchymal progenitor cells from the periosteum and surrounding tissues to form the cartilaginous and bony calluses. The proinflammatory cytokine interleukin (IL)-17 family has gained attention for its potential regenerative effects; however, the requirement of IL-17 signaling within mesenchymal progenitor cells for normal secondary fracture healing remains unknown. The conditional knockout of IL-17 receptor a (<i>Il17ra</i>) in mesenchymal progenitor cells was achieved by crossing <i>Il17ra</i><sup>F/F</sup> mice with <i>Prx1-cre</i> mice to generate <i>Prx1-cre</i>; <i>Il17ra</i><sup>F/F</sup> mice. At 3 months of age, mice underwent experimental unilateral mid-diaphyseal femoral fractures and healing was assessed by micro-computed tomography (µCT) and histomorphometric analyses. The effects of IL-17RA signaling on the osteogenic differentiation of fracture-activated periosteal cells was investigated in vitro. Examination of the intact skeleton revealed that the conditional knockout of <i>Il17ra</i> decreased the femoral cortical porosity but did not affect any femoral trabecular microarchitectural indices. After unilateral femoral fractures, <i>Il17ra</i> conditional knockout impacted the cartilage and bone composition of the fracture callus that was most evident early in the healing process (day 7 and 14 post-fracture). Furthermore, the in vitro treatment of fracture-activated periosteal cells with IL-17A inhibited osteogenesis. This study suggests that IL-17RA signaling within <i>Prx1</i>+ mesenchymal progenitor cells can influence the early stages of endochondral ossification during fracture healing.https://www.mdpi.com/1422-0067/25/7/3751periosteumsecondary bone healingIL-17Ainflammationcytokine |
| spellingShingle | Joseph L. Roberts David Kapfhamer Varsha Devarapalli Hicham Drissi IL-17RA Signaling in Prx1+ Mesenchymal Cells Influences Fracture Healing in Mice International Journal of Molecular Sciences periosteum secondary bone healing IL-17A inflammation cytokine |
| title | IL-17RA Signaling in Prx1+ Mesenchymal Cells Influences Fracture Healing in Mice |
| title_full | IL-17RA Signaling in Prx1+ Mesenchymal Cells Influences Fracture Healing in Mice |
| title_fullStr | IL-17RA Signaling in Prx1+ Mesenchymal Cells Influences Fracture Healing in Mice |
| title_full_unstemmed | IL-17RA Signaling in Prx1+ Mesenchymal Cells Influences Fracture Healing in Mice |
| title_short | IL-17RA Signaling in Prx1+ Mesenchymal Cells Influences Fracture Healing in Mice |
| title_sort | il 17ra signaling in prx1 mesenchymal cells influences fracture healing in mice |
| topic | periosteum secondary bone healing IL-17A inflammation cytokine |
| url | https://www.mdpi.com/1422-0067/25/7/3751 |
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