Kuroyanagi G(1)(2)(3), Sakai G(4)(5)(6), Otsuka T(4), Yamamoto N(4)(5), Fujita K(4)(5), Kawabata T(4)(5), Matsushima-Nishiwaki R(5), Kozawa O(5), Tokuda H(5)(7). Author information:
(1)Department of Orthopedic Surgery, Nagoya City University Graduate School of
Medical Sciences, 1 Kawasumi, Micuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
[Email]
(2)Department of Rehabilitation Medicine, Nagoya City University Graduate School
of Medical Sciences, Nagoya, 467-8601, Japan. [Email]
(3)Department of Pharmacology, Gifu University Graduate School of Medicine,
Gifu, 501-1194, Japan. [Email]
(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.
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.
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