Unilateral Hypofunction of the Masseter Leads to Molecular and 3D Morphometric Signs of Atrophy in Ipsilateral Agonist Masticatory Muscles in Adult Mice.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Masticatory Muscles* ; Botulinum Toxins, Type A*; Adult ; Humans ; Mice ; Male ; Animals ; Myogenin ; Masseter Muscle/pathology ; Masseter Muscle/physiology ; Muscular Atrophy/pathology ; RNA, Messenger

Mice are commonly used to study mandibular dynamics due to their similarity in chewing cycle patterns with humans. Adult mice treated unilaterally with botulinum toxin type A (BoNTA) in the masseter exhibit atrophy of this muscle characterized by an increase in the gene expression of atrophy-related molecular markers, and a reduction in both muscle fiber diameter and muscle mass at 14d. However, the impact of this muscle imbalance on the non-treated masticatory muscles remains unexplored. Here, we hypothesize that the unilateral masseter hypofunction leads to molecular and 3D morphometric signs of atrophy of the masseter and its agonist masticatory muscles in adult mice. Twenty-three 8-week-old male BALB/c mice received a single injection of BoNTA in the right masseter, whereas the left masseter received the same volume of saline solution (control side). Animals were euthanized at 2d, 7d, and 14d, and the masticatory muscles were analyzed for mRNA expression. Five heads were harvested at 14d, fixed, stained with a contrast-enhanced agent, and scanned using X-ray microtomography. The three-dimensional morphometric parameters (the volume and thickness) from muscles in situ were obtained. Atrogin-1/MAFbx , MuRF-1, and Myogenin mRNA gene expression were significantly increased at 2 and 7d for both the masseter and temporalis from the BoNTA side. For medial pterygoid, increased mRNA gene expression was found at 7d for Atrogin-1/MAFbx and at 2d-7d for Myogenin . Both the volume and thickness of the masseter, temporalis, and medial pterygoid muscles from the BoNTA side were significantly reduced at 14d. In contrast, the lateral pterygoid from the BoNTA side showed a significant increase in volume at 14d. Therefore, the unilateral hypofunction of the masseter leads to molecular and morphological signs of atrophy in both the BoNTA-injected muscle and its agonistic non-injected masticatory muscles. The generalized effect on the mouse masticatory apparatus when one of its components is intervened suggests the need for more clinical studies to determine the safety of BoNTA usage in clinical dentistry.

J Oral Rehabil. 2019 Mar;46(3):233-241. (PMID: 30468522)
J Int Med Res. 2011;39(2):378-87. (PMID: 21672341)
J Dent Res. 2003 Apr;82(4):318-21. (PMID: 12651939)
Int J Environ Res Public Health. 2021 Sep 10;18(18):. (PMID: 34574476)
Dent Clin North Am. 2023 Apr;67(2):335-348. (PMID: 36965935)
BMC Oral Health. 2021 Oct 14;21(1):527. (PMID: 34649558)
Front Physiol. 2017 May 09;8:273. (PMID: 28536534)
Behav Res Methods. 2007 May;39(2):175-91. (PMID: 17695343)
Bone. 2020 May;134:115301. (PMID: 32112989)
J Anat. 2013 Jul;223(1):46-60. (PMID: 23692055)
Ann Anat. 2018 Mar;216:112-119. (PMID: 29289710)
Pharmacol Rev. 2017 Apr;69(2):200-235. (PMID: 28356439)
Int J Environ Res Public Health. 2022 Nov 23;19(23):. (PMID: 36497634)
Dis Model Mech. 2012 Jul;5(4):533-45. (PMID: 22563056)
Cureus. 2022 Aug 19;14(8):e28167. (PMID: 36158329)
PLoS One. 2014 Jul 07;9(7):e101379. (PMID: 25000590)
Biomed Eng Online. 2019 May 16;18(1):59. (PMID: 31096969)
J Oral Facial Pain Headache. 2021 Fall;35(4):288-296. (PMID: 34990497)
Toxins (Basel). 2020 Jun 15;12(6):. (PMID: 32549196)
J Oral Rehabil. 2023 Aug;50(8):706-714. (PMID: 37078711)
Clin Oral Investig. 2021 Feb;25(2):441-453. (PMID: 33409693)
Nat Commun. 2020 Nov 4;11(1):5577. (PMID: 33149150)
J Craniomaxillofac Surg. 2022 Jan;50(1):7-18. (PMID: 34620536)
Int J Mol Sci. 2022 Aug 21;23(16):. (PMID: 36012713)
Brain Sci. 2023 Mar 12;13(3):. (PMID: 36979291)
Front Cell Neurosci. 2021 Jun 30;15:663384. (PMID: 34276308)
J Oral Rehabil. 2023 Sep 5;:. (PMID: 37668276)
Am J Physiol Endocrinol Metab. 2014 Apr 15;306(8):E869-82. (PMID: 24518675)
Calcif Tissue Int. 2018 Jun;102(6):695-704. (PMID: 29222689)
Cell. 2010 Oct 1;143(1):35-45. (PMID: 20887891)
J Dent Res. 2019 Dec;98(13):1450-1457. (PMID: 31533008)
J Cell Biochem. 2011 Aug;112(8):2149-59. (PMID: 21465538)
Dent Clin North Am. 2023 Apr;67(2):211-225. (PMID: 36965927)
Nucleic Acids Res. 2001 May 1;29(9):e45. (PMID: 11328886)
Evid Based Dent. 2022 May 27;:. (PMID: 35624296)
J Oral Rehabil. 2020 Mar;47(3):395-402. (PMID: 31769044)
Toxins (Basel). 2019 Feb 01;11(2):. (PMID: 30717172)
J Bone Miner Res. 2023 Jan;38(1):5-13. (PMID: 36301601)
Ann Anat. 2021 Jul;236:151715. (PMID: 33675949)
Nat Methods. 2012 Jul;9(7):671-5. (PMID: 22930834)
Toxins (Basel). 2022 Jun 29;14(7):. (PMID: 35878179)
Front Endocrinol (Lausanne). 2021 Mar 01;11:606947. (PMID: 33732211)
Am J Orthod Dentofacial Orthop. 2019 Aug;156(2):193-202. (PMID: 31375229)
J Prosthet Dent. 2022 Jun 29;:. (PMID: 35779974)
J Oral Rehabil. 2017 May;44(5):363-374. (PMID: 28181679)

1151353 Fondecyt Program - ANID Chile; 1201385 Fondecyt Program - ANID Chile; 1190406 Fondecyt Program - ANID Chile; 1231103 Fondecyt Program - ANID Chile; 11150175 Fondecyt Program - ANID Chile; 21170015 CONYCIT Scholarship - ANID Chile; no number Max Planck Society; no number Universidad del Valle School of Dentistry

Keywords: X-ray microtomography; botulinum toxins; masticatory muscles; muscular atrophy; type A

0 (Myogenin)
EC 3.4.24.69 (Botulinum Toxins, Type A)
0 (RNA, Messenger)

Date Created: 20231014 Date Completed: 20231023 Latest Revision: 20231023

20231215

PMC10572689

10.3390/ijms241914740

37834190