Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth
Authors: Shufang Wu
Wei Yang
Francesco De Luca
Journal: Endocrinology (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: GH; growth plate chondrogenesis; longitudinal bone growth; IGF-1; IGF-2
Affiliations: Section of Endocrinology and Diabetes (S.W., F.D.L.), St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, Pennsylvania 19134; and Center for Translational Medicine (S.W., W.Y.), the First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, People's Republic of China.

Abstract:  GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated (TamCart)Igf1r(flox/flox) mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. (TamCart)Igf1r(flox/flox) tamoxifen-treated mice [knockout (KO) mice] and their Igf1r(flox/flox) control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-Œ∫B p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects. 

Retracted: No

PubPeer comments:
 Figure 6A. Much more similar than you would expect. https: imgur.com 6VPcJgX , 
 Figure 7B. Much more similar than you would expect. https: imgur.com ShCOXWv , 
 Figure 1A. * Red boxes: In the Cre panels, the  Wild type and  IGF-1R Floxed lanes look unexpectedly similar. * Green boxes: In the middle panels, the  Growth plate and  Wild type lanes look unexpectedly similar. * Blue boxes: In the bottom panesl, the  Liver and  IGF-1R Floxed lanes look unexpectedly similar. A possible cut might be visible between the  Heart and  Liver lanes.  Here is a false-color rendering of Figure 1A, without markers, but showing the similarities in the grey scales.  , 
 https: pubpeer.com publications 70278FC3FE87F93815BA3DF7D59B51#2 Withdrawal of a paper with overlapping authorship for similar issues. ,