Abstract
Herein, we investigate the high incidence of umbilical hernia and tippy-toe standing and their underlying changes in gene expression and proliferation in myostatin knockout (MSTN−/−) pigs. Thirty-six male MSTN−/− pigs were generated by somatic cell nuclear transfer (SCNT). These pigs presented a considerably high incidence of tippy-toe standing and umbilical hernia (69.4% and 61.1%, respectively). The tendon to body weight ratio was significantly lower than wild-type pigs (0.202 ± 0.017 vs 0.250 ± 0.004, respectively). The crimp length of the MSTN−/− tendon was significantly longer than that of wild-type pigs. The expression of MSTN and the activin type IIB (ACVR2B) was detected in the tendon and linea alba of MSTN−/− pigs. MSTN treatment significantly increased the phosphorylation of Smad2/3 in both tendon and linea alba fibroblasts. Type I collagen (Col1A) and Scleraxis (Scx) expression levels in the tendon and linea alba of MSTN−/− pigs were significantly lower than those in wild-type in vivo, whereas and cyclin-dependent kinase inhibitor 1 (p21) expression levels were higher. Treatment of tendon and linea alba fibroblasts with recombinant MSTN increased Col1A and Scx and decreased p21 expression in vivo. Moreover, there was a significant increase in fibroblast proliferation after treatment. The results indicated that MSTN regulates collagen expression and proliferation in tendon and linea alba fibroblasts; thus, MSTN deficiency causes collagen-related pathological features in MSTN−/− pigs. Hence, MSTN could be used as a therapeutic target for treating UH and tendon abnormalities.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
The authors thank all the staff at the Longxing Pig Farm (Longjing, China) for their assistance with feeding and care of the animals.
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This work was supported by the National Natural Science Foundation of China (No. 31860297).
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All authors contributed to the writing, review, and editing. H.-J. Paek contributed to conception and design of the study, writing of the manuscript; H.-J. Paek and Z.-B. Luo collected the field samples; H.-M. Choe, K. Gao, S.-Z. Han, and Z.-Y. Li performed experiments and collected the data; J.-D. Kang and B.-H. Quan analyzed the data statistically; X.-J. Yin provided regarding supervision and funding support. All authors approved the final version of the manuscript.
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Paek, HJ., Luo, ZB., Choe, HM. et al. Association of myostatin deficiency with collagen related disease-umbilical hernia and tippy toe standing in pigs. Transgenic Res 30, 663–674 (2021). https://doi.org/10.1007/s11248-021-00275-6
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DOI: https://doi.org/10.1007/s11248-021-00275-6