Display options
Cite
Wacker MJ, Touchberry CD, Silswal N, et al. Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets. Front Physiol. 2016;7:173doi: 10.3389/fphys.2016.00173.
Wacker, M. J., Touchberry, C. D., Silswal, N., Brotto, L., Elmore, C. J., Bonewald, L. F., Andresen, J., & Brotto, M. (2016). Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets. Frontiers in physiology, 7173. https://doi.org/10.3389/fphys.2016.00173
Wacker, Michael J, et al. "Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets." Frontiers in physiology vol. 7 (2016): 173. doi: https://doi.org/10.3389/fphys.2016.00173
Wacker MJ, Touchberry CD, Silswal N, Brotto L, Elmore CJ, Bonewald LF, Andresen J, Brotto M. Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets. Front Physiol. 2016 May 13;7:173. doi: 10.3389/fphys.2016.00173. eCollection 2016. PMID: 27242547; PMCID: PMC4866514.
Copy Download .nbib Format: NLM
Share it on

Front Physiol. 2016 May 13;7:173. doi: 10.3389/fphys.2016.00173. eCollection 2016.

Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets.

Frontiers in physiology

Michael J Wacker, Chad D Touchberry, Neerupma Silswal, Leticia Brotto, Chris J Elmore, Lynda F Bonewald, Jon Andresen, Marco Brotto

Affiliations

  1. Muscle Biology Research Group, School of Medicine, University of Missouri-Kansas City Kansas City, MO, USA.
  2. School of Health Studies, University of Memphis Memphis, TN, USA.
  3. Bone-Muscle Collaborative Science, College of Nursing and Health Innovation, University of Texas at Arlington Arlington, TX, USA.
  4. Bone Biology Research Group, School of Dentistry, University of Missouri-Kansas City Kansas City, MO, USA.

PMID: 27242547 PMCID: PMC4866514 DOI: 10.3389/fphys.2016.00173

Abstract

Autosomal recessive hypophosphatemic rickets (ARHR) is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well-characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand in order to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL-fast-twitch muscle), soleus (SOL-slow-twitch muscle), heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum) which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2α or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In summary, these results indicate that there are deficiencies in both fast twitch and slow twitch muscle fiber type contractions in this model of ARHR, while there was less of a phenotype observed in cardiac muscle, and no differences observed in aortic function. These results may help explain skeletal muscle weakness reported by some patients with osteomalacia and need to be further investigated.

Keywords: Autosomal recessive hypophosphatemic rickets; DMP1; bone-muscle crosstalk; cardiac muscle; cardiovascular disease; osteomalacia; sarcopenia; skeletal muscle

References

  1. Aging (Albany NY). 2011 Jun;3(6):621-34 - PubMed
  2. J Dent Res. 2003 Oct;82(10):776-80 - PubMed
  3. J Clin Endocrinol Metab. 1997 Aug;82(8):2450-4 - PubMed
  4. Bone. 2015 Nov;80:37-42 - PubMed
  5. J Bone Miner Res. 2011 Feb;26(2):331-40 - PubMed
  6. Am J Physiol Endocrinol Metab. 2013 Apr 15;304(8):E863-73 - PubMed
  7. Annu Rev Physiol. 2007;69:341-59 - PubMed
  8. J Bone Miner Res. 1990 May;5(5):469-74 - PubMed
  9. Am J Physiol Endocrinol Metab. 2014 Sep 1;307(5):E426-36 - PubMed
  10. Bone. 2014 Sep;66:82-9 - PubMed
  11. Bonekey Rep. 2014 Jun 04;3:543 - PubMed
  12. J Clin Invest. 1983 Aug;72(2):582-9 - PubMed
  13. J Biol Chem. 2014 Aug 1;289(31):21533-43 - PubMed
  14. J Clin Invest. 1976 Apr;57(4):1019-24 - PubMed
  15. FASEB J. 2011 Aug;25(8):2551-62 - PubMed
  16. J Biol Chem. 2010 Dec 17;285(51):40312-21 - PubMed
  17. Nephrol Dial Transplant. 2014 Aug;29(8):1525-32 - PubMed
  18. Curr Osteoporos Rep. 2014 Sep;12(3):252-62 - PubMed
  19. J Bone Miner Metab. 2004;22(5):430-8 - PubMed
  20. Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2016-26 - PubMed
  21. J Bone Miner Res. 2005 Dec;20(12):2169-77 - PubMed
  22. J Musculoskelet Neuronal Interact. 2005 Oct-Dec;5(4):325-7 - PubMed
  23. Kidney Int. 1983 Jul;24(1):53-7 - PubMed
  24. Mol Endocrinol. 2012 Nov;26(11):1883-95 - PubMed
  25. Kidney Int. 2013 Jun;83(6):1159-68 - PubMed
  26. JACC Heart Fail. 2014 Aug;2(4):380-9 - PubMed
  27. J Clin Endocrinol Metab. 2012 Aug;97(8):E1492-8 - PubMed
  28. J Vis Exp. 2012 Nov 01;(69):e4198 - PubMed
  29. Cell Metab. 2015 Dec 1;22(6):1020-32 - PubMed
  30. J Bone Miner Res. 2011 Apr;26(4):803-10 - PubMed
  31. J Clin Invest. 2011 Nov;121(11):4393-408 - PubMed
  32. Clin Rev Bone Miner Metab. 2014 Jun;12(2):77-85 - PubMed
  33. Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2216-25 - PubMed
  34. J Bone Miner Res. 2004 Mar;19(3):429-35 - PubMed
  35. Nat Genet. 2006 Nov;38(11):1310-5 - PubMed
  36. Arch Biochem Biophys. 2010 Aug 15;500(2):157-61 - PubMed
  37. Lancet. 1976 Mar 20;1(7960):626-9 - PubMed
  38. Bone. 2013 Jun;54(2):213-21 - PubMed
  39. J Clin Endocrinol Metab. 2013 May;98 (5):E990-5 - PubMed
  40. Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E254-61 - PubMed
  41. Eur J Pharmacol. 2008 Jun 10;587(1-3):243-7 - PubMed
  42. Bone. 2009 Feb;44(2):287-94 - PubMed
  43. Cell Cycle. 2015 ;14 (10 ):1507-16 - PubMed
  44. J Biol Chem. 2016 Feb 26;291(9):4308-22 - PubMed
  45. Recent Pat Biotechnol. 2012 Dec;6(3):223-9 - PubMed
  46. Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1636-44 - PubMed
  47. J Biol Chem. 2004 Apr 30;279(18):19141-8 - PubMed
  48. J Biomol Tech. 2005 Sep;16(3):266-71 - PubMed
  49. J Bone Miner Res. 2010 Oct;25(10):2165-74 - PubMed
  50. Am J Hum Genet. 2010 Feb 12;86(2):267-72 - PubMed
  51. PPAR Res. 2012;2012:302495 - PubMed
  52. J Biol Chem. 2005 Feb 18;280(7):6197-203 - PubMed
  53. Curr Osteoporos Rep. 2014 Jun;12(2):135-41 - PubMed
  54. J Clin Invest. 1989 Sep;84(3):990-5 - PubMed

Publication Types