Del1 Is a Growth Factor for Skeletal Progenitor Cells in the Fracture Callus
Failure to properly form bone or integrate surgical implants can lead to morbidity and additional surgical interventions in a significant proportion of orthopedic surgeries. While the role of skeletal stem cells (SSCs) in bone formation and repair is well-established, very little is known about the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/8/1214 |
| _version_ | 1827730244020207616 |
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| author | Yuxi Sun Tatiana Boyko Owen Marecic Danielle Struck Randall K. Mann Tom W. Andrew Michael Lopez Xinming Tong Stuart B. Goodman Fan Yang Michael T. Longaker Charles K. F. Chan George P. Yang |
| author_facet | Yuxi Sun Tatiana Boyko Owen Marecic Danielle Struck Randall K. Mann Tom W. Andrew Michael Lopez Xinming Tong Stuart B. Goodman Fan Yang Michael T. Longaker Charles K. F. Chan George P. Yang |
| author_sort | Yuxi Sun |
| collection | DOAJ |
| description | Failure to properly form bone or integrate surgical implants can lead to morbidity and additional surgical interventions in a significant proportion of orthopedic surgeries. While the role of skeletal stem cells (SSCs) in bone formation and repair is well-established, very little is known about the factors that regulate the downstream Bone, Cartilage, Stromal, Progenitors (BCSPs). BCSPs, as transit amplifying progenitor cells, undergo multiple mitotic divisions to expand the pool of lineage committed progenitors allowing stem cells to preserve their self-renewal and stemness. Del1 is a protein widely expressed in the skeletal system, but its deletion led to minimal phenotype changes in the uninjured mouse. In this paper, we demonstrate that Del1 is a key regulator of BCSP expansion following injury. In Del1 knockout mice, there is a significant reduction in the number of BCSPs which leads to a smaller callus and decreased bone formation compared with wildtype (WT) littermates. Del1 serves to promote BCSP proliferation and prevent apoptosis in vivo and in vitro. Moreover, exogenous Del1 promotes proliferation of aged human BCSPs. Our results highlight the potential of Del1 as a therapeutic target for improving bone formation and implant success. Del1 injections may improve the success of orthopedic surgeries and fracture healing by enhancing the proliferation and survival of BCSPs, which are crucial for generating new bone tissue during the process of bone formation and repair. |
| first_indexed | 2024-03-11T00:05:29Z |
| format | Article |
| id | doaj.art-7d8597179e964c4cb89170a7aed4ad0d |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T00:05:29Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-7d8597179e964c4cb89170a7aed4ad0d2023-11-19T00:23:49ZengMDPI AGBiomolecules2218-273X2023-08-01138121410.3390/biom13081214Del1 Is a Growth Factor for Skeletal Progenitor Cells in the Fracture CallusYuxi Sun0Tatiana Boyko1Owen Marecic2Danielle Struck3Randall K. Mann4Tom W. Andrew5Michael Lopez6Xinming Tong7Stuart B. Goodman8Fan Yang9Michael T. Longaker10Charles K. F. Chan11George P. Yang12Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USADivision of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USADivision of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USADivision of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USADivision of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USADivision of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USADivision of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Orthopedic Surgery, Stanford University, Stanford, CA 94305, USADepartment of Orthopedic Surgery, Stanford University, Stanford, CA 94305, USADepartment of Orthopedic Surgery, Stanford University, Stanford, CA 94305, USADivision of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USADivision of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USAFailure to properly form bone or integrate surgical implants can lead to morbidity and additional surgical interventions in a significant proportion of orthopedic surgeries. While the role of skeletal stem cells (SSCs) in bone formation and repair is well-established, very little is known about the factors that regulate the downstream Bone, Cartilage, Stromal, Progenitors (BCSPs). BCSPs, as transit amplifying progenitor cells, undergo multiple mitotic divisions to expand the pool of lineage committed progenitors allowing stem cells to preserve their self-renewal and stemness. Del1 is a protein widely expressed in the skeletal system, but its deletion led to minimal phenotype changes in the uninjured mouse. In this paper, we demonstrate that Del1 is a key regulator of BCSP expansion following injury. In Del1 knockout mice, there is a significant reduction in the number of BCSPs which leads to a smaller callus and decreased bone formation compared with wildtype (WT) littermates. Del1 serves to promote BCSP proliferation and prevent apoptosis in vivo and in vitro. Moreover, exogenous Del1 promotes proliferation of aged human BCSPs. Our results highlight the potential of Del1 as a therapeutic target for improving bone formation and implant success. Del1 injections may improve the success of orthopedic surgeries and fracture healing by enhancing the proliferation and survival of BCSPs, which are crucial for generating new bone tissue during the process of bone formation and repair.https://www.mdpi.com/2218-273X/13/8/1214fracture healingbone regenerationskeletal progenitor cellsDel1proliferation |
| spellingShingle | Yuxi Sun Tatiana Boyko Owen Marecic Danielle Struck Randall K. Mann Tom W. Andrew Michael Lopez Xinming Tong Stuart B. Goodman Fan Yang Michael T. Longaker Charles K. F. Chan George P. Yang Del1 Is a Growth Factor for Skeletal Progenitor Cells in the Fracture Callus Biomolecules fracture healing bone regeneration skeletal progenitor cells Del1 proliferation |
| title | Del1 Is a Growth Factor for Skeletal Progenitor Cells in the Fracture Callus |
| title_full | Del1 Is a Growth Factor for Skeletal Progenitor Cells in the Fracture Callus |
| title_fullStr | Del1 Is a Growth Factor for Skeletal Progenitor Cells in the Fracture Callus |
| title_full_unstemmed | Del1 Is a Growth Factor for Skeletal Progenitor Cells in the Fracture Callus |
| title_short | Del1 Is a Growth Factor for Skeletal Progenitor Cells in the Fracture Callus |
| title_sort | del1 is a growth factor for skeletal progenitor cells in the fracture callus |
| topic | fracture healing bone regeneration skeletal progenitor cells Del1 proliferation |
| url | https://www.mdpi.com/2218-273X/13/8/1214 |
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