Article (Scientific journals)
Osteocyte-derived insulin-like growth factor I is essential for determining bone mechanosensitivity
Lau, K.-H. William; Baylink, David J.; Zhou, Xiao-Dong et al.
2013In American Journal of Physiology - Endocrinology and Metabolism, 305 (2), p. 271-E281
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Keywords :
osteocytes; insulin-like growth factor I; mechanical loading; mechanotransduction; Wnt
Abstract :
[en] This study sought to determine whether deficient Igf1 expression in osteocytes would affect loading-induced osteogenic response. Tibias of osteocyte Igf1 conditional knockout (KO) mice (generated by crossbreeding Igf1 floxed mice with Dmp1-Cre transgenic mice) and wild-type (WT) littermates were subjected to four-point bending for 2 wk. Microcomputed tomography confirmed that the size of tibias of conditional mutants was smaller. Loading with an equivalent loading strain increased periosteal woven bone and endosteal lamellar bone formation in WT mice but not in conditional KO mice. Consistent with the lack of an osteogenic response, the loading failed to upregulate expression of early mechanoresponsive genes (Igf1, Cox-2, c-fos) or osteogenic genes (Cbfa-1, and osteocalcin) in conditional KO bones. The lack of osteogenic response was not due to reduced osteocyte density or insufficient loading strain. Deficient osteocyte Igf1 expression reduced the loading-induced upregulation of expression of canonical Wnt signaling genes (Wnt10b, Lrp5, Dkk1, sFrp2). The loading also reduced (by 40%) Sost expression in WT mice, but the loading not only did not reduce but upregulated (similar to 1.5-fold) Sost expression in conditional KO mice. Conditional disruption of Igf1 in osteocytes also abolished the loading-induced increase in the bone beta-catenin protein level. These findings suggest an impaired response in the loading-induced upregulation of the Wnt signaling in conditional KO mice. In summary, conditional disruption of Igf1 in osteocytes abolished the loading-induced activation of the Wnt signaling and the corresponding osteogenic response. In conclusion, osteocyte-derived IGF-I plays a key determining role in bone mechanosensitivity.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Endocrinology, metabolism & nutrition
Author, co-author :
Lau, K.-H. William;  Loma Linda Univ, Sch Med, Dept Med, Div Regenerat Med, Loma Linda, CA 92350 USA.
Baylink, David J.;  Loma Linda Univ, Sch Med, Dept Med, Div Regenerat Med, Loma Linda, CA 92350 USA.
Zhou, Xiao-Dong;  Loma Linda Univ, Sch Med, Dept Med, Div Regenerat Med, Loma Linda, CA 92350 USA.
Rodriguez, Denise;  Loma Linda Univ, Sch Med, Dept Med, Div Regenerat Med, Loma Linda, CA 92350 USA.
Bonewald, Lynda F.;  Univ Missouri, Kansas City Dent Sch, Dept Oral Biol, Kansas City, MO 64110 USA.
Li, Zihui;  ETH, Inst Biomech, Zurich, Switzerland.
Ruffoni, Davide  ;  Université de Liège - ULiège > Département d'aérospatiale et mécanique > Mécanique des matériaux biologiques et bioinspirés
Mueller, Ralph;  ETH, Inst Biomech, Zurich, Switzerland.
Kesavan, Chandrasekhar;  Jerry L Pettis Mem Vet Affairs Med Ctr, Musculoskeletal Dis Ctr, Loma Linda, CA USA.
Sheng, Matilda H.-C.;  Loma Linda Univ, Sch Med, Dept Med, Div Regenerat Med, Loma Linda, CA 92350 USA.
Language :
English
Title :
Osteocyte-derived insulin-like growth factor I is essential for determining bone mechanosensitivity
Publication date :
2013
Journal title :
American Journal of Physiology - Endocrinology and Metabolism
ISSN :
0193-1849
eISSN :
1522-1555
Publisher :
Amer Physiological Soc, Bethesda, United States - Maryland
Volume :
305
Issue :
2
Pages :
E271-E281
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Telemedicine and Advanced Technology Research Center (TATRC) at the US Army Medical Research and Material Command (USAMRMC) [W81XWH-08-1-0697]
Commentary :
The work is supported by the Telemedicine and Advanced Technology Research Center (TATRC) at the US Army Medical Research and Material Command (USAMRMC) under Grant No. W81XWH-08-1-0697. The views, opinions and/or findings contained in this report are those of the authors and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation.
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