Journal article
Does Riluzole Influence Bone Formation?: An In Vitro Study of Human Mesenchymal Stromal Cells and Osteoblast.
- Schroeder GD Department of Orthopaedic Surgery, The Rothman Institute at Thomas Jefferson University, Philadelphia, PA.
- Kepler CK Department of Orthopaedic Surgery, The Rothman Institute at Thomas Jefferson University, Philadelphia, PA.
- Grad S AO Research Institute Davos, Davos, Switzerland.
- Alini M AO Research Institute Davos, Davos, Switzerland.
- Fang T Department of Orthopaedic Surgery, The Rothman Institute at Thomas Jefferson University, Philadelphia, PA.
- Markova DZ Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA.
- Koerner JD Department of Orthopaedic Surgery, Hackensack University Medical Center, Hackensack, NJ.
- Rajasekaran S Ganga Hospital, Coimbatore, Tamil Nadu, India.
- Chapman J The Swedish Neuroscience Institute, Seattle, WA.
- Kandziora F Berufsgenossenschaftliche Unfallklinik Frankfurt, Center for Spinal Surgery and Neurotraumatology, Frankfurt am Main, Germany.
- Schnake KJ Schön Klinik Nürnberg Fürth, Center for Spinal Surgery, Fürth, Germany.
- Dvorak MF Department of Orthopaedics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
- Oner FC Department of Orthopaedics, University Medical Center, Utrecht, the Netherlands.
- Vaccaro AR Department of Orthopaedic Surgery, The Rothman Institute at Thomas Jefferson University, Philadelphia, PA.
- 2019-03-22
Published in:
- Spine. - 2019
Alkaline Phosphatase
Cell Differentiation
Cells, Cultured
Collagen Type I
Fracture Healing
Humans
Mesenchymal Stem Cells
Osteoblasts
Osteocalcin
Osteogenesis
Riluzole
English
STUDY DESIGN
A post-test design biological experiment.
OBJECTIVE
The aim of this study was to evaluate the osteogenic effects of riluzole on human mesenchymal stromal cells and osteoblasts.
SUMMARY OF BACKGROUND DATA
Riluzole may benefit patients with spinal cord injury (SCI) from a neurologic perspective, but little is known about riluzole's effect on bone formation, fracture healing, or osteogenesis.
METHODS
Human mesenchymal stromal cells (hMSCs) and human osteoblasts (hOB) were obtained and isolated from healthy donors and cultured. The cells were treated with riluzole of different concentrations (50, 150, 450 ng/mL) for 1, 2, 3, and 4 weeks. Cytotoxicity was evaluated as was the induction of osteogenic differentiation of hMSCs. Differentiation was evaluated by measuring alkaline phosphatase (ALP) activity and with Alizarin red staining. Osteogenic gene expression of type I collagen (Col1), ALP, osteocalcin (Ocn), Runx2, Sox9, Runx2/Sox9 ratio were measured by qRT-PCR.
RESULTS
No cytotoxicity or increased proliferation was observed in bone marrow derived hMSCs and primary hOBs cultured with riluzole over 7 days. ALP activity was slightly increased in hMSCs after treatment for 2 weeks with riluzole 150 ng/mL and slightly upregulated by 150% (150 ng/mL) and 90% (450 ng/mL) in hMSCs at 3 weeks. In hOBs, ALP activity almost doubled after 2 weeks of culture with riluzole 150 ng/mL (P < 0.05). More pronounced 2.6-fold upregulation was noticed after 3 weeks of culture with riluzole at both 150 ng/mL (P = 0.05) and 450 ng/mL (P = 0.05). No significant influence of riluzole on the mRNA expression of osteocalcin (OCN) was observed.
CONCLUSION
The effect of riluzole on bone formation is mixed; low-dose riluzole has no effect on the viability or function of either hMSCs or hOBs. The activity of ALP in both cell types is upregulated by high-dose riluzole, which may indicate that high-dose riluzole can increase osteogenic metabolism and subsequently accelerate bone healing process. However, at high concentrations, riluzole leads to a decrease in osteogenic gene expression, including Runx2 and type 1 collagen.
LEVEL OF EVIDENCE
N/A.
A post-test design biological experiment.
OBJECTIVE
The aim of this study was to evaluate the osteogenic effects of riluzole on human mesenchymal stromal cells and osteoblasts.
SUMMARY OF BACKGROUND DATA
Riluzole may benefit patients with spinal cord injury (SCI) from a neurologic perspective, but little is known about riluzole's effect on bone formation, fracture healing, or osteogenesis.
METHODS
Human mesenchymal stromal cells (hMSCs) and human osteoblasts (hOB) were obtained and isolated from healthy donors and cultured. The cells were treated with riluzole of different concentrations (50, 150, 450 ng/mL) for 1, 2, 3, and 4 weeks. Cytotoxicity was evaluated as was the induction of osteogenic differentiation of hMSCs. Differentiation was evaluated by measuring alkaline phosphatase (ALP) activity and with Alizarin red staining. Osteogenic gene expression of type I collagen (Col1), ALP, osteocalcin (Ocn), Runx2, Sox9, Runx2/Sox9 ratio were measured by qRT-PCR.
RESULTS
No cytotoxicity or increased proliferation was observed in bone marrow derived hMSCs and primary hOBs cultured with riluzole over 7 days. ALP activity was slightly increased in hMSCs after treatment for 2 weeks with riluzole 150 ng/mL and slightly upregulated by 150% (150 ng/mL) and 90% (450 ng/mL) in hMSCs at 3 weeks. In hOBs, ALP activity almost doubled after 2 weeks of culture with riluzole 150 ng/mL (P < 0.05). More pronounced 2.6-fold upregulation was noticed after 3 weeks of culture with riluzole at both 150 ng/mL (P = 0.05) and 450 ng/mL (P = 0.05). No significant influence of riluzole on the mRNA expression of osteocalcin (OCN) was observed.
CONCLUSION
The effect of riluzole on bone formation is mixed; low-dose riluzole has no effect on the viability or function of either hMSCs or hOBs. The activity of ALP in both cell types is upregulated by high-dose riluzole, which may indicate that high-dose riluzole can increase osteogenic metabolism and subsequently accelerate bone healing process. However, at high concentrations, riluzole leads to a decrease in osteogenic gene expression, including Runx2 and type 1 collagen.
LEVEL OF EVIDENCE
N/A.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1097/BRS.0000000000003022
- PMID 30896584
- Persistent URL
- https://sonar.ch/global/documents/278777
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