Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system

Hironori Hojo; Fumiko Yano; Shinsuke Ohba; Kazuyo Igawa; Keiji Nakajima; Yuske Komiyama; Akinori Kan; Toshiyuki Ikeda; Takayuki Yonezawa; Je-Tae Woo; Tsuyoshi Takato; Kozo Nakamura; Hiroshi Kawaguchi; Ung-il Chung

doi:10.1007/s00774-010-0179-y

Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system

J Bone Miner Metab. 2010 Nov;28(6):627-33. doi: 10.1007/s00774-010-0179-y. Epub 2010 Apr 8.

Authors

Hironori Hojo¹, Fumiko Yano, Shinsuke Ohba, Kazuyo Igawa, Keiji Nakajima, Yuske Komiyama, Akinori Kan, Toshiyuki Ikeda, Takayuki Yonezawa, Je-Tae Woo, Tsuyoshi Takato, Kozo Nakamura, Hiroshi Kawaguchi, Ung-il Chung

Affiliation

¹ Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. hojo@bmw.t.u-tokyo.ac.jp

PMID: 20376510
DOI: 10.1007/s00774-010-0179-y

Abstract

To effectively treat degenerative joint diseases including osteoarthritis (OA), small chemical compounds need to be developed that can potently induce chondrogenic differentiation without promoting terminal differentiation. For this purpose, we screened natural and synthetic compound libraries using a Col2GFP-ATDC5 system and identified oxytetracycline (Oxy) as a chondrogenic compound. Oxy induced cartilaginous matrix synthesis and mRNA expressions of chondrocyte markers in ATDC5 cells. In addition, Oxy suppressed mineralization and mRNA expressions of terminal chondrocyte differentiation markers in ATDC5 cells, primary chondrocytes, and cultured metatarsal bones. Oxy's induction of Col2 mRNA expression was decreased by the addition of Noggin and was increased by the addition of BMP2. Furthermore, Oxy increased mRNA expression of Id1, Bmp2, Bmp4, and Bmp6. These data suggest that Oxy induces chondrogenic differentiation in a BMP-dependent manner and suppresses terminal differentiation. Oxy may be useful for treatment of OA and also for regeneration of cartilage tissue.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Differentiation / genetics
Antigens, Differentiation / metabolism
Bone Morphogenetic Proteins / antagonists & inhibitors
Bone Morphogenetic Proteins / genetics
Bone Morphogenetic Proteins / metabolism
Cell Differentiation / drug effects*
Cell Line
Cells, Cultured
Chondrocytes / cytology
Chondrocytes / drug effects*
Chondrocytes / metabolism
Collagen Type II / genetics
Collagen Type II / metabolism
Drug Evaluation, Preclinical
Embryo, Mammalian
Gene Expression Regulation / drug effects
High-Throughput Screening Assays
Inhibitor of Differentiation Protein 1 / genetics
Inhibitor of Differentiation Protein 1 / metabolism
Metatarsal Bones / drug effects
Metatarsal Bones / metabolism
Mice
Mice, Inbred C57BL
Osteoarthritis / drug therapy
Osteogenesis / drug effects*
Oxytetracycline / pharmacology*
RNA, Messenger / metabolism
Small Molecule Libraries
Tissue Culture Techniques

Substances

Antigens, Differentiation
Bone Morphogenetic Proteins
Col2a1 protein, mouse
Collagen Type II
Idb1 protein, mouse
Inhibitor of Differentiation Protein 1
RNA, Messenger
Small Molecule Libraries
Oxytetracycline