Locally delivered lovastatin nanoparticles enhance fracture healing in rats

Garrett, I. Ross; Gutiérrez, Gloria; Rossini, Gianni; Nyman, Jeffry S.; McCluskey, Brandon; Flores, Alda; Mundy, Gregory R.

doi:10.1002/jor.20391

Cited by 78 publications

(81 citation statements)

References 20 publications

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“…Consequently, studies on topical application of statins have been performed. These studies are consistent and report likewise improved fracture healing in rodents treated with statins topically (Skoglund and Aspenberg, 2007, Wang et al, 2007, Garrett et al, 2007.…”

Section: Study I: Statinssupporting

confidence: 79%

Use of medications and risk of revision after primary total hip arthroplasty

Thillemann¹

2009

Acta Orthopaedica

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Section: Study I: Statinssupporting

confidence: 79%

Use of medications and risk of revision after primary total hip arthroplasty

Thillemann¹

2009

Acta Orthopaedica

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“…Osseous tissue includes an organic matrix such as collagen and complex minerals including calcium, phosphate, carbonate, citrate, hydroxyl, and sodium. Concerns regarding nanotoxicity to bone tissue have been raised due to the increased exposure of humans to nanoparticles and to the application of nanomedicine to the treatment of bone diseases such as osteoporosis, 359,360 bone fractures, 361,362 and other bone disorders 361 and in dentistry. 363,364 In these applications, nanoparticles replace directly natural bone tissue or are remineralized and resorbed into bones to facilitate bone growth or recovery.…”

Section: Nanotoxicity To Bonesmentioning

confidence: 99%

Perturbation of physiological systems by nanoparticles

et al. 2014

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Nanotechnology is having a tremendous impact on our society. However, societal concerns about human safety under nanoparticle exposure may derail the broad application of this promising technology. Nanoparticles may enter the human body via various routes, including respiratory pathways, the digestive tract, skin contact, intravenous injection, and implantation. After absorption, nanoparticles are carried to distal organs by the bloodstream and the lymphatic system. During this process, they interact with biological molecules and perturb physiological systems. Although some ingested or absorbed nanoparticles are eliminated, others remain in the body for a long time. The human body is composed of multiple systems that work together to maintain physiological homeostasis. The unexpected invasion of these systems by nanoparticles disturbs normal cell signaling, impairs cell and organ functions, and may even cause pathological disorders. This review examines the comprehensive health risks of exposure to nanoparticles by discussing how nanoparticles perturb various physiological systems as revealed by animal studies. The potential toxicity of nanoparticles to each physiological system and the implications of disrupting the balance among systems are emphasized.

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“…Radiographic analysis was performed to assess healing parameters using a Faxitron x-ray machine (MX-20 Specimen Radiography System; Faxitron Bioptics, LLC, Tucson, AZ, USA). Radiographs were captured at multiple time-points post-fracture (7, 28 and 42 days) and were assessed blindly by three independent investigators using the scoring scale described previously (10). The scale was obtained according to rebridgement (no rebridgement, partial or complete) and the results were expressed as a percentage alteration from saline-treated groups (saline-treated =100%).…”

Section: Introductionmentioning

confidence: 99%

Effect of CoCl2 on fracture repair in a rat model of bone fracture

Huang

Liu

Feng

et al. 2015

Molecular Medicine Reports

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Abstract. Low oxygen availability is known to activate the hypoxia-inducible factor-1α (HIF-1α) pathway, which is involved in the impairment of fracture healing. However, the role of low oxygen in fracture healing remains to be fully elucidated. In the present study, rats were divided into two groups and treated with CoCl 2 or saline, respectively. Rats with tibial fractures were sacrificed at 14, 28 and 42 days subsequent to fracture. Autoradiography was performed to measure healing of the bone tissue. In addition, the effects of cobalt chloride (CoCl 2 ) on the expression of two major angiogenic mediators, HIF-1α and vascular endothelial growth factor (VEGF), as well as the osteoblast markers runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OC) were determined at mRNA and protein levels by reverse transcription-quantitative polymerase chain reaction, western blot analysis and immunohistochemistry. Systemic administration of CoCl 2 (15 mg/ kg/day intraperitoneally) significantly promoted fracture healing and mechanical strength. The present study demonstrated that in rats treated with CoCl 2 , the expression of HIF-1α, VEGF, Runx2, ALP and OC was significantly increased at mRNA and protein levels, and that CoCl 2 treatment enhances fracture repair in vivo. IntroductionTraumatic fractures are the most common type of injury in daily life. In the majority of clinical cases, the most simple fractures heal with minimal intervention; however, in severe fractures and in certain patient populations, including diabetics and patients with splintered fractures, impaired fracture healing and bone defects occur (1,2). In spite of numerous advances in every discipline of medicine, patients with complex bone injuries of the upper and lower extremities and are required to undergo prolonged reconstructive procedures for retrieval of their limb functions (2,3).It has been reported that the hypoxia-inducible factor (HIF) pathway is the central pathway for sensing and responding to alterations in local oxygen levels in a wide variety of organisms (4). Activation of the HIF-1α pathway can act as a critical mediator of neoangiogenesis, which is required for skeletal regeneration; thus, it is suggested that the application of HIF activators may be used as therapies to improve bone healing (4). An increasing number of studies suggested that hypoxia may be a powerful stimulus for bone cells via the mediation of angiogenesis [vascular endothelial growth factor (VEGF)], cellular metabolism (glucose transporter) and the recruitment of mesenchymal cells (MSCs) to areas of matrix damage (5-7). A more thorough understanding of hypoxia in bone healing will lead to the elucidation of cellular and molecular mechanisms that may aid in the development of protective therapies. CoCl 2 , a mimic of hypoxia, directly enhances HIF-1α stabilization and downstream target genes by inhibiting prolyl hydroxylase enzymes (8). An improved understanding of the alterations in gene expression that occur during fracture he...

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Locally delivered lovastatin nanoparticles enhance fracture healing in rats

Cited by 78 publications

References 20 publications

Use of medications and risk of revision after primary total hip arthroplasty

Use of medications and risk of revision after primary total hip arthroplasty

Perturbation of physiological systems by nanoparticles

Effect of CoCl2 on fracture repair in a rat model of bone fracture

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