Gen Kuroyanagi1,2,3, Go Sakai4,5,6, Takanobu Otsuka4, Naohiro Yamamoto4,5, Kazuhiko Fujita4,5, Tetsu Kawabata4,5, Rie Matsushima-Nishiwaki5, Osamu Kozawa5, Haruhiko Tokuda5,7. 1. Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Micuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. kokuryugen@yahoo.co.jp. 2. Department of Rehabilitation Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan. kokuryugen@yahoo.co.jp. 3. Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan. kokuryugen@yahoo.co.jp. 4. Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Micuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. 5. Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan. 6. Department of Orthopedic Surgery, Komaki City Hospital, Komaki, 485-8520, Japan. 7. Department of Clinical Laboratory/Biobank of Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, 474-8511, Japan.
Abstract
BACKGROUND: Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells. METHODS: MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting. RESULTS: The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation. CONCLUSIONS: Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.
BACKGROUND:Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells. METHODS:MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting. RESULTS: The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation. CONCLUSIONS: Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.
Authors: Harm H Kampinga; Jurre Hageman; Michel J Vos; Hiroshi Kubota; Robert M Tanguay; Elspeth A Bruford; Michael E Cheetham; Bin Chen; Lawrence E Hightower Journal: Cell Stress Chaperones Date: 2008-07-29 Impact factor: 3.667
Authors: Joy Irobi; Katrien Van Impe; Pavel Seeman; Albena Jordanova; Ines Dierick; Nathalie Verpoorten; Andrej Michalik; Els De Vriendt; An Jacobs; Veerle Van Gerwen; Krist'l Vennekens; Radim Mazanec; Ivailo Tournev; David Hilton-Jones; Kevin Talbot; Ivo Kremensky; Ludo Van Den Bosch; Wim Robberecht; Joël Van Vandekerckhove; Christine Van Broeckhoven; Jan Gettemans; Peter De Jonghe; Vincent Timmerman Journal: Nat Genet Date: 2004-05-02 Impact factor: 38.330