title: Therapeutic potentials of naringin on polymethylmethacrylate induced osteoclastogenesis and osteolysis, in vitro and in vivo assessments.
abstract: Wear debris associated periprosthetic osteolysis represents a major pathological process associated with the aseptic loosening of joint prostheses. Naringin is a major flavonoid identified in grapefruit. Studies have shown that naringin possesses many pharmacological properties including effects on bone metabolism. The current study evaluated the influence of naringin on wear debris induced osteoclastic bone resorption both in vitro and in vivo. The osteoclast precursor cell line RAW 264.7 was cultured and stimulated with polymethylmethacrylate (PMMA) particles followed by treatment with naringin at several doses. Tartrate resistant acid phosphatase (TRAP), calcium release, and gene expression profiles of TRAP, cathepsin K, and receptor activator of nuclear factor-kappa B were sequentially evaluated. PMMA challenged murine air pouch and the load bearing tibia titanium pin-implantation mouse models were used to evaluate the effects of naringin in controlling PMMA induced bone resorption. Histological analyses and biomechanical pullout tests were performed following the animal experimentation. The in vitro data clearly demonstrated the inhibitory effects of naringin in PMMA induced osteoclastogenesis. The naringin dose of 10 μg/mL exhibited the most significant influence on the suppression of TRAP activities. Naringin treatment also markedly decreased calcium release in the stimulated cell culture medium. The short-term air pouch mouse study revealed that local injection of naringin ameliorated the PMMA induced inflammatory tissue response and subsequent bone resorption. The long-term tibia pin-implantation mouse model study suggested that daily oral gavage of naringin at 300 mg/kg dosage for 30 days significantly alleviated the periprosthetic bone resorption. A significant increase of periprosthetic bone volume and regaining of the pin stability were found in naringin treated mice. Overall, this study suggests that naringin may serve as a potential therapeutic agent to treat wear debris associated osteolysis.
authors.affiliation: Department of Surgery, Orthopedics, University of Kansas School of Medicine, Wichita, KS, USA ; Department of Orthopedics, Affiliated Hospital to Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China.
authors.forename: Nianhu
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Affiliated Hospital to Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China.
authors.forename: Zhanwang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Surgery, Orthopedics, University of Kansas School of Medicine, Wichita, KS, USA ; Orthopaedic Research Institute, Via Christi Wichita Hospitals, Wichita, KS, USA.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Wooley
authors.affiliation: Department of Orthopedics, Affiliated Hospital to Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Orthopedics, University of Kansas School of Medicine, Wichita, KS, USA ; Orthopaedic Research Institute, Via Christi Wichita Hospitals, Wichita, KS, USA.
authors.forename: Shang-You
authors.initials: SY
authors.lastname: Yang
mesh_terms: D000135:Acid Phosphatase / Q000037:antagonists & inhibitors; D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects*; D010014:Osteolysis / Q000517:prevention & control*; D019904:Polymethyl Methacrylate / Q000633:toxicity*; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D044950:Flavanones; D007527:Isoenzymes; D019904:Polymethyl Methacrylate; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; C005274:naringin; D002118:Calcium
keywords: aseptic loosening; naringin; osteoclastogenesis; periprosthetic osteolysis