Elimination of BMP7 from the developing limb mesenchyme leads to articular cartilage degeneration and synovial inflammation with increased age

被引:35
作者
Abula, Kahaer [1 ]
Muneta, Takeshi [1 ]
Miyatake, Kazumasa [1 ]
Yamada, Jun [1 ]
Matsukura, Yu [1 ]
Inoue, Makiko [1 ]
Sekiya, Ichiro [2 ]
Graf, Daniel [3 ]
Economides, Aris N. [4 ]
Rosen, Vicki [5 ]
Tsuji, Kunikazu [6 ]
机构
[1] Tokyo Med & Dent Univ, Grad Sch, Dept Joint Surg & Sports Med, Tokyo 1138519, Japan
[2] Tokyo Med & Dent Univ, Ctr Stem Cell & Regenerat Med, Tokyo, Japan
[3] Univ Alberta, Sch Dent, Edmonton, AB T6G 2M7, Canada
[4] Regeneron Pharmaceut Inc, Tarrytown, NY USA
[5] Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02138 USA
[6] Tokyo Med & Dent Univ, Grad Sch, Dept Cartilage Regenerat, Tokyo, Japan
基金
日本学术振兴会;
关键词
Bone morphogenetic protein 7; Articular cartilage; Synovitis; Proteoglycan; Activin A; Osteoarthritis; DISCOID LATERAL-MENISCUS; TERM-FOLLOW-UP; OSTEOGENIC PROTEIN-1; BONE-FORMATION; KNEE OSTEOARTHRITIS; TOTAL MENISCECTOMY; CHICK LIMB; FRACTURE; MICE; CHONDROCYTES;
D O I
10.1016/j.febslet.2015.04.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
While osteo- and chondro-inductive activities of recombinant human bone morphogenetic protein 7 are well established, evaluation of the role of endogenous BMP7 in skeletal homeostasis has been hampered by perinatal lethality in BMP7 knockout mice. Here, we examined physiological roles of endogenous BMP7 in joint homeostasis and showed that proteoglycan contents in articular cartilage were significantly reduced in the absence of BMP7. Loss of BMP7 did not affect survival of articular cartilage cells, but resulted in reduced expression of aggrecan and enhanced expression of matrix metalloproteinase 13. We also found extensive synovial hyperplasia and enhanced expression of Activin A. These findings suggest that locally produced BMP7 is prerequisite for postnatal synovial joint homeostasis and may be involved in osteoarthritic changes in adults. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1240 / 1248
页数:9
相关论文
共 45 条
[31]   A Longitudinal Analysis of Urinary Biochemical Markers and Bone Mineral Density in STR/Ort Mice as a Model of Spontaneous Osteoarthritis [J].
Sarukawa, Junichiro ;
Takahashi, Masaaki ;
Doi, Mitsuhito ;
Suzuki, Daisuke ;
Nagano, Akira .
ARTHRITIS AND RHEUMATISM, 2010, 62 (02) :463-471
[32]   The role of synovitis in osteoarthritis pathogenesis [J].
Scanzello, Carla R. ;
Goldring, Steven R. .
BONE, 2012, 51 (02) :249-257
[33]   Immunohistological Localization of BMP-2, BMP-7, and Their Receptors in Knee Joints with Focal Cartilage Lesions [J].
Schmal, Hagen ;
Mehlhorn, Alexander T. ;
Pilz, Ingo H. ;
Dovi-Akue, David ;
Kirchhoff, Christina ;
Suedkamp, Norbert P. ;
Gerlach, Ulrike ;
Lohrmann, Christian ;
Niemeyer, Philipp .
SCIENTIFIC WORLD JOURNAL, 2012,
[34]   Periodic Knee Injections of BMP-7 Delay Cartilage Degeneration Induced by Excessive Running in Rats [J].
Sekiya, Ichiro ;
Tang, Tao ;
Hayashi, Masaya ;
Morito, Toshiyuki ;
Ju, Young-Jin ;
Mochizuki, Tomoyuki ;
Muneta, Takeshi .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2009, 27 (08) :1088-1092
[35]   Epidemiology of osteoarthritis: an update [J].
Sharma, L ;
Kapoor, D ;
Issa, S .
CURRENT OPINION IN RHEUMATOLOGY, 2006, 18 (02) :147-156
[36]  
Solloway MJ, 1998, DEV GENET, V22, P321, DOI 10.1002/(SICI)1520-6408(1998)22:4<321::AID-DVG3>3.3.CO
[37]  
2-7
[38]   BMP-7 inhibits cartilage degeneration through suppression of inflammation in rat zymosan-induced arthritis [J].
Takahashi, Toru ;
Muneta, Takeshi ;
Tsuji, Kunikazu ;
Sekiya, Ichiro .
CELL AND TISSUE RESEARCH, 2011, 344 (02) :321-332
[39]   BMP4 is dispensable for skeletogenesis and fracture-healing in the limb [J].
Tsuji, Kunikazu ;
Cox, Karen ;
Bandyopadhyay, Amitabha ;
Harfe, Brian D. ;
Tabin, Clifford J. ;
Rosen, Vicki .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 2008, 90A :14-18
[40]   BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing [J].
Tsuji, Kunikazu ;
Bandyopadhyay, Amitabha ;
Harfe, Brian D. ;
Cox, Karen ;
Kakar, Sanjeev ;
Gerstenfeld, Louis ;
Einhorn, Thomas ;
Tabin, Clifford J. ;
Rosen, Vicki .
NATURE GENETICS, 2006, 38 (12) :1424-1429