The effects of targeted deliveries of lovastatin and tocotrienol on ossification-related gene expressions in fracture healing in an osteoporosis rat model

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Abstract

Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II–VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 μg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 μg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 μg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing.

Original languageEnglish
Pages (from-to)12958-12976
Number of pages19
JournalInternational Journal of Environmental Research and Public Health
Volume12
Issue number10
DOIs
Publication statusPublished - 16 Oct 2015

Fingerprint

Tocotrienols
Lovastatin
Fracture Healing
Osteogenesis
Osteoporosis
Gene Expression
Postmenopausal Osteoporosis
Injections
Osteocalcin
Tibia
Vascular Endothelial Growth Factor A
Sprague Dawley Rats
Estrogens
Pharmaceutical Preparations

Keywords

  • Fracture healing genes
  • Lovastatin
  • Osteoporotic fracture healing
  • Targeted delivery
  • Tocotrienol

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

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title = "The effects of targeted deliveries of lovastatin and tocotrienol on ossification-related gene expressions in fracture healing in an osteoporosis rat model",
abstract = "Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II–VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 μg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 μg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 μg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing.",
keywords = "Fracture healing genes, Lovastatin, Osteoporotic fracture healing, Targeted delivery, Tocotrienol",
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T1 - The effects of targeted deliveries of lovastatin and tocotrienol on ossification-related gene expressions in fracture healing in an osteoporosis rat model

AU - Ibrahim, Nurul Izzah

AU - Mohamed, Norazlina

AU - Soelaiman, Ima Nirwana

AU - Shuid, Ahmad Nazrun

PY - 2015/10/16

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N2 - Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II–VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 μg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 μg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 μg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing.

AB - Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II–VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 μg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 μg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 μg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing.

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