TY - JOUR
T1 - Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system
AU - Hojo, Hironori
AU - Yano, Fumiko
AU - Ohba, Shinsuke
AU - Igawa, Kazuyo
AU - Nakajima, Keiji
AU - Komiyama, Yuske
AU - Kan, Akinori
AU - Ikeda, Toshiyuki
AU - Yonezawa, Takayuki
AU - Woo, Je Tae
AU - Takato, Tsuyoshi
AU - Nakamura, Kozo
AU - Kawaguchi, Hiroshi
AU - Chung, Ung Il
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - BMP
KW - Chondrocyte differentiation
KW - Col2GFP-ATDC5
KW - Osteoarthritis
KW - Small compound
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U2 - 10.1007/s00774-010-0179-y
DO - 10.1007/s00774-010-0179-y
M3 - Article
C2 - 20376510
AN - SCOPUS:78349310936
SN - 0914-8779
VL - 28
SP - 627
EP - 633
JO - Journal of Bone and Mineral Metabolism
JF - Journal of Bone and Mineral Metabolism
IS - 6
ER -