Abstract
Aims
Stanniocalcin-2 (STC2) has recently been implicated in human muscle mass variability by genetic analysis. Biochemically, STC2 inhibits the proteolytic activity of the metalloproteinase PAPP-A, which promotes muscle growth by upregulating the insulin-like growth factor (IGF) axis. The aim was to examine if STC2 affects skeletal muscle mass and to assess how the IGF axis mediates muscle hypertrophy induced by functional overload.
Methods
We compared muscle mass and muscle fiber morphology between Stc2−/− (n = 21) and wild-type (n = 15) mice. We then quantified IGF1, IGF2, IGF binding proteins −4 and −5 (IGFBP-4, IGFBP-5), PAPP-A and STC2 in plantaris muscles of wild-type mice subjected to 4-week unilateral overload (n = 14).
Results
Stc2−/− mice showed up to 10% larger muscle mass compared with wild-type mice. This increase was mediated by greater cross-sectional area of muscle fibers. Overload increased plantaris mass and components of the IGF axis, including quantities of IGF1 (by 2.41-fold, p = 0.0117), IGF2 (1.70-fold, p = 0.0461), IGFBP-4 (1.48-fold, p = 0.0268), PAPP-A (1.30-fold, p = 0.0154) and STC2 (1.28-fold, p = 0.019).
Conclusion
Here we provide evidence that STC2 is an inhibitor of muscle growth upregulated, along with other components of the IGF axis, during overload-induced muscle hypertrophy.
Stanniocalcin-2 (STC2) has recently been implicated in human muscle mass variability by genetic analysis. Biochemically, STC2 inhibits the proteolytic activity of the metalloproteinase PAPP-A, which promotes muscle growth by upregulating the insulin-like growth factor (IGF) axis. The aim was to examine if STC2 affects skeletal muscle mass and to assess how the IGF axis mediates muscle hypertrophy induced by functional overload.
Methods
We compared muscle mass and muscle fiber morphology between Stc2−/− (n = 21) and wild-type (n = 15) mice. We then quantified IGF1, IGF2, IGF binding proteins −4 and −5 (IGFBP-4, IGFBP-5), PAPP-A and STC2 in plantaris muscles of wild-type mice subjected to 4-week unilateral overload (n = 14).
Results
Stc2−/− mice showed up to 10% larger muscle mass compared with wild-type mice. This increase was mediated by greater cross-sectional area of muscle fibers. Overload increased plantaris mass and components of the IGF axis, including quantities of IGF1 (by 2.41-fold, p = 0.0117), IGF2 (1.70-fold, p = 0.0461), IGFBP-4 (1.48-fold, p = 0.0268), PAPP-A (1.30-fold, p = 0.0154) and STC2 (1.28-fold, p = 0.019).
Conclusion
Here we provide evidence that STC2 is an inhibitor of muscle growth upregulated, along with other components of the IGF axis, during overload-induced muscle hypertrophy.
| Original language | English |
|---|---|
| Article number | e15793 |
| Number of pages | 12 |
| Journal | Physiological reports |
| Volume | 11 |
| Issue number | 15 |
| Early online date | 11 Aug 2023 |
| DOIs | |
| Publication status | Published - 11 Aug 2023 |
Bibliographical note
ACKNOWLEDGMENTSThe authors gratefully acknowledge the Microscopy and Histology Core Facility for their support and assistance in this work. The work presented here was supported as follows. AL: Awards AR052879 and AR056280 from the National Institute of Arthritis, Musculoskeletal and Skin Diseases; award 249156 from the FP7-PEOPLE-2009-RG programme, award CGA/18/05 from the Chief Scientist Office, award 21/019 from the NHS Grampian Research Endowment. AL, GSB and LKH: award 204815/Z/16/Z from the Wellcome Trust. AIHC: The Providence Airway Centre, the St. Paul's Foundation and the Michael Smith Foundation for Health Research trainee award (RT-2021-1591). LKH: Biotechnology and Biological Sciences Research Council (BB/R01857X/1, BB/V016849/1). CO: Independent Research Fund Denmark (201930362460).
Keywords
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- biologging
- prey reduction
- northern fulmar
- ecosystem effects
- fisheries interactions