Interference by adrenaline with chondrogenic differentiation through suppression of gene transactivation mediated by Sox9 family members |
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| Authors: | Takeshi Takarada Hironori Hojo Mika Iemata Koichi Sahara Ayumi Kodama Nobuhiro Nakamura Eiichi Hinoi Yukio Yoneda |
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| Affiliation: | 1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Japan;2. Department of Hematology, Kainan Hospital, Yatomi City, Japan;3. Department of Medical Oncology, Nagoya Memorial Hospital, Nagoya City, Japan;4. Department of Hematology, Aichi Medical University, Nagakute City, Japan;5. Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Japan;6. Technology Development, Section 1, Research & Development Department, SRL Inc., Hino-city, Japan;1. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States;2. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States;3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States;1. OncoRay – National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Germany;2. Department of Radiotherapy and Oncology, University of Frankfurt, Germany;3. Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus, Dresden University of Technology, Germany;1. Department of In Vitro Carcinogenesis and Cellular Chemotherapy (IVCCC), Chittaranjan National Cancer Institute, Kolkata, India;2. Department of Pharmacology, Institute of Post Graduate Medical Education and Research, Kolkata, India |
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| Abstract: | In contrast to osteoblasts, little attention has been paid to the functional expression of adrenergic signaling machineries in chondrocytes. Expression of mRNA was for the first time demonstrated for different adrenergic receptor (AdR) subtypes in chondrogenic ATDC5 cells and mouse metatarsals isolated before vascularization in culture, but not for other molecules related to adrenergic signaling. In neonatal mouse tibial sections, β2AdR and α2aAdR mRNA expression was found in chondrocytes at different developmental stages by in situ hybridization. Exposure to adrenaline significantly suppressed expression of several maturation markers through the cAMP/protein kinase A pathway activated by β2AdR without affecting cellular proliferation in both cultured ATDC5 cells and metatarsals. Adrenaline also significantly inhibited gene transactivation by sry-type HMG box 9 (Sox9) family members essential for chondrogenic differentiation in a manner prevented by the general βAdR antagonist propranolol, with a concomitant significant decrease in the levels of Sox6 mRNA and corresponding protein, in ATDC5 cells and primary cultured mouse costal chondrocytes. Systemic administration of propranolol significantly promoted the increased expression of mRNA for collagen I and collagen X, but not for collagen II, in callus of fractured femur in mice. These results suggest that adrenaline may interfere with chondrogenic differentiation through downregulation of Sox6 expression for subsequent suppression of gene transactivation mediated by Sox9 family members after activation of β2AdR expressed by chondrocytes. |
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