TY - JOUR
T1 - The role of Tsukushi (TSK), a small leucine-rich repeat proteoglycan, in bone growth
AU - Yano, Kosei
AU - Washio, Kaoru
AU - Tsumanuma, Yuka
AU - Yamato, Masayuki
AU - Ohta, Kunimasa
AU - Okano, Teruo
AU - Izumi, Yuichi
N1 - Funding Information:
The authors thank Takanori Iwata of the Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, for excellent expert advice; Terumasa Umemoto of the International Research Center for Medical Science, Kumamoto University, for valuable advice and suggestions; Mami Kokubo of the Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, for technical support; Masaki Noda of 1. Tokyo Medical and Dental University, 2. Yokohama City Minato Red Cross Hospital, for practical advice; Yoichi Ezura of Tokyo Medical and Dental University, for technical support and advice; Kazuhiro Aoki of Tokyo Medical and Dental University, for advice and suggestions; This study was partially supported by the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems “Cell Sheet Tissue Engineering Center (CSTEC)” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan .
Funding Information:
The authors thank Takanori Iwata of the Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, for excellent expert advice; Terumasa Umemoto of the International Research Center for Medical Science, Kumamoto University, for valuable advice and suggestions; Mami Kokubo of the Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, for technical support; Masaki Noda of 1. Tokyo Medical and Dental University, 2. Yokohama City Minato Red Cross Hospital, for practical advice; Yoichi Ezura of Tokyo Medical and Dental University, for technical support and advice; Kazuhiro Aoki of Tokyo Medical and Dental University, for advice and suggestions; This study was partially supported by the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems “Cell Sheet Tissue Engineering Center (CSTEC)” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.
Publisher Copyright:
© 2017 The Japanese Society for Regenerative Medicine
PY - 2017/12
Y1 - 2017/12
N2 - Introduction Endochondral ossification is one of a key process for bone maturation. Tsukushi (TSK) is a novel member of the secreted small leucine-rich repeat proteoglycan (SLRP) family. SLRPs localize to skeletal regions and play significant roles during whole phases of bone development. Although prior evidence suggests that TSK may be involved in the regulation of bone formation, its role in skeletal development has not yet been elucidated. Methods In the present study, we examined TSK's function during bone growth by comparing skeletal growth of TSK deficient (TSK−/−) mice and wild type (WT) mice. And an in vitro experiment using siRNA transfection of a chondrogenic cell line was performed. Results TSK−/− mice exhibited decreased weight and short stature at 3 weeks of age due to decreased longitudinal bone growth coupled with low bone mass. Furthermore, an in vitro experiment using siRNA transfection into a chondrogenic cell line revealed that decreased TSK expression induced down-regulation of key chondrogenic marker gene expression and up-regulation of mid-to-late chondrogenic markers gene expression. Conclusions Our results reveal that TSK regulates bone elongation and bone mass by modulating growth plate chondrocyte function and consequently, overall body size.
AB - Introduction Endochondral ossification is one of a key process for bone maturation. Tsukushi (TSK) is a novel member of the secreted small leucine-rich repeat proteoglycan (SLRP) family. SLRPs localize to skeletal regions and play significant roles during whole phases of bone development. Although prior evidence suggests that TSK may be involved in the regulation of bone formation, its role in skeletal development has not yet been elucidated. Methods In the present study, we examined TSK's function during bone growth by comparing skeletal growth of TSK deficient (TSK−/−) mice and wild type (WT) mice. And an in vitro experiment using siRNA transfection of a chondrogenic cell line was performed. Results TSK−/− mice exhibited decreased weight and short stature at 3 weeks of age due to decreased longitudinal bone growth coupled with low bone mass. Furthermore, an in vitro experiment using siRNA transfection into a chondrogenic cell line revealed that decreased TSK expression induced down-regulation of key chondrogenic marker gene expression and up-regulation of mid-to-late chondrogenic markers gene expression. Conclusions Our results reveal that TSK regulates bone elongation and bone mass by modulating growth plate chondrocyte function and consequently, overall body size.
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U2 - 10.1016/j.reth.2017.08.001
DO - 10.1016/j.reth.2017.08.001
M3 - Article
AN - SCOPUS:85041049087
SN - 2352-3204
VL - 7
SP - 98
EP - 107
JO - Regenerative Therapy
JF - Regenerative Therapy
ER -