Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells
Abstract
Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 (Sostdc1–/–) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1–/– cortical bone measurements revealed larger bones with higher BMD, suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1–/– mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3 days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1–/– 5 day calluses harbor > 2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callusmore »
- Publication Date:
- Research Org.:
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1315852
- Alternate Identifier(s):
- OSTI ID: 1377772
- Report Number(s):
- LLNL-JRNL-658875
Journal ID: ISSN 8756-3282; S8756328216300904; PII: S8756328216300904
- Grant/Contract Number:
- 11-ERD-060; AC52-07NA27344
- Resource Type:
- Published Article
- Journal Name:
- Bone
- Additional Journal Information:
- Journal Name: Bone Journal Volume: 88 Journal Issue: C; Journal ID: ISSN 8756-3282
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Collette, Nicole M., Yee, Cristal S., Hum, Nicholas R., Murugesh, Deepa K., Christiansen, Blaine A., Xie, LiQin, Economides, Aris N., Manilay, Jennifer O., Robling, Alexander G., and Loots, Gabriela G. Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells. United States: N. p., 2016.
Web. doi:10.1016/j.bone.2016.04.005.
Collette, Nicole M., Yee, Cristal S., Hum, Nicholas R., Murugesh, Deepa K., Christiansen, Blaine A., Xie, LiQin, Economides, Aris N., Manilay, Jennifer O., Robling, Alexander G., & Loots, Gabriela G. Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells. United States. https://doi.org/10.1016/j.bone.2016.04.005
Collette, Nicole M., Yee, Cristal S., Hum, Nicholas R., Murugesh, Deepa K., Christiansen, Blaine A., Xie, LiQin, Economides, Aris N., Manilay, Jennifer O., Robling, Alexander G., and Loots, Gabriela G. Fri .
"Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells". United States. https://doi.org/10.1016/j.bone.2016.04.005.
@article{osti_1315852,
title = {Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells},
author = {Collette, Nicole M. and Yee, Cristal S. and Hum, Nicholas R. and Murugesh, Deepa K. and Christiansen, Blaine A. and Xie, LiQin and Economides, Aris N. and Manilay, Jennifer O. and Robling, Alexander G. and Loots, Gabriela G.},
abstractNote = {Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 (Sostdc1–/–) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1–/– cortical bone measurements revealed larger bones with higher BMD, suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1–/– mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3 days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1–/– 5 day calluses harbor > 2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callus formation and bone repair. Elevated numbers of MSCs in D5 calluses resulted in a larger, more vascularized cartilage callus at day 7, and a more rapid turnover of cartilage with significantly more remodeled bone and a thicker cortical shell at 21 days post fracture. In conclusion, these data support accelerated or enhanced bone formation/remodeling of the callus in Sostdc1–/– mice, suggesting that Sostdc1 may promote and maintain mesenchymal stem cell quiescence in the periosteum.},
doi = {10.1016/j.bone.2016.04.005},
journal = {Bone},
number = C,
volume = 88,
place = {United States},
year = {Fri Jul 01 00:00:00 EDT 2016},
month = {Fri Jul 01 00:00:00 EDT 2016}
}
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https://doi.org/10.1016/j.bone.2016.04.005
https://doi.org/10.1016/j.bone.2016.04.005
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Cited by: 25 works
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