Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects
Lipoteichoic acid (LTA) is a cell wall component of Gram-positive bacteria. Limited data suggest that LTA is beneficial for bone regeneration in vitro. Thus, we used a mouse model of femoral defects to explore the effects of LTA on bone healing in vivo. Micro-computed tomography analysis and double-...
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2020-08-01
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author | Chih-Chien Hu Chih-Hsiang Chang Yi-min Hsiao Yuhan Chang Ying-Yu Wu Steve W. N. Ueng Mei-Feng Chen |
author_facet | Chih-Chien Hu Chih-Hsiang Chang Yi-min Hsiao Yuhan Chang Ying-Yu Wu Steve W. N. Ueng Mei-Feng Chen |
author_sort | Chih-Chien Hu |
collection | DOAJ |
description | Lipoteichoic acid (LTA) is a cell wall component of Gram-positive bacteria. Limited data suggest that LTA is beneficial for bone regeneration in vitro. Thus, we used a mouse model of femoral defects to explore the effects of LTA on bone healing in vivo. Micro-computed tomography analysis and double-fluorochrome labeling were utilized to examine whether LTA can accelerate dynamic bone formation in vivo. The effects of LTA on osteoblastogenesis and osteoclastogenesis were also studied in vitro. LTA treatment induced prompt bone bridge formation, rapid endochondral ossification, and accelerated healing of fractures in mice with femoral bone defects. In vitro, LTA directly enhanced indicators of osteogenic factor-induced MC3T3-E1 cell differentiation, including alkaline phosphatase activity, calcium deposition and osteopontin expression. LTA also inhibited osteoclast activation induced by receptor activator of nuclear factor-kappa B ligand. We identified six molecules that may be associated with LTA-accelerated bone healing: monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 1, cystatin C, growth/differentiation factor 15, endostatin and neutrophil gelatinase-associated lipocalin. Finally, double-fluorochrome, dynamic-labeling data indicated that LTA significantly enhanced bone-formation rates in vivo. In conclusion, our findings suggest that LTA has promising bone-regeneration properties. |
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language | English |
last_indexed | 2024-03-10T18:00:15Z |
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spelling | doaj.art-abd0efc55ec4483fa58ee50ddf41e2282023-11-20T08:55:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012115555010.3390/ijms21155550Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral DefectsChih-Chien Hu0Chih-Hsiang Chang1Yi-min Hsiao2Yuhan Chang3Ying-Yu Wu4Steve W. N. Ueng5Mei-Feng Chen6Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanBone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanLipoteichoic acid (LTA) is a cell wall component of Gram-positive bacteria. Limited data suggest that LTA is beneficial for bone regeneration in vitro. Thus, we used a mouse model of femoral defects to explore the effects of LTA on bone healing in vivo. Micro-computed tomography analysis and double-fluorochrome labeling were utilized to examine whether LTA can accelerate dynamic bone formation in vivo. The effects of LTA on osteoblastogenesis and osteoclastogenesis were also studied in vitro. LTA treatment induced prompt bone bridge formation, rapid endochondral ossification, and accelerated healing of fractures in mice with femoral bone defects. In vitro, LTA directly enhanced indicators of osteogenic factor-induced MC3T3-E1 cell differentiation, including alkaline phosphatase activity, calcium deposition and osteopontin expression. LTA also inhibited osteoclast activation induced by receptor activator of nuclear factor-kappa B ligand. We identified six molecules that may be associated with LTA-accelerated bone healing: monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 1, cystatin C, growth/differentiation factor 15, endostatin and neutrophil gelatinase-associated lipocalin. Finally, double-fluorochrome, dynamic-labeling data indicated that LTA significantly enhanced bone-formation rates in vivo. In conclusion, our findings suggest that LTA has promising bone-regeneration properties.https://www.mdpi.com/1422-0067/21/15/5550lipoteichoic acidbone healingfemoral defectfracturealkaline phosphataseosteopontin |
spellingShingle | Chih-Chien Hu Chih-Hsiang Chang Yi-min Hsiao Yuhan Chang Ying-Yu Wu Steve W. N. Ueng Mei-Feng Chen Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects International Journal of Molecular Sciences lipoteichoic acid bone healing femoral defect fracture alkaline phosphatase osteopontin |
title | Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects |
title_full | Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects |
title_fullStr | Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects |
title_full_unstemmed | Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects |
title_short | Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects |
title_sort | lipoteichoic acid accelerates bone healing by enhancing osteoblast differentiation and inhibiting osteoclast activation in a mouse model of femoral defects |
topic | lipoteichoic acid bone healing femoral defect fracture alkaline phosphatase osteopontin |
url | https://www.mdpi.com/1422-0067/21/15/5550 |
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