ATP2A2 Associates with Masseter Fiber Composition in Class II Malocclusion

Objectives: We previously reported that the strength-related gene ATP2A2, is down- regulated in masseter muscle of malocclusion subjects with facial asymmetry. Because ATP2A2 (a.k.a. SERCA2) is an ATP-dependent calcium channel protein in sarcoplasmic reticulum associated with slow type-I muscle fibers, we tested for correlations between its expression and type-I, fast type-IIA and hybrid-I/II fiber composition in masseter muscles of patients with craniofacial disorders.
Methods: Twenty subjects with non-syndromic dentofacial deformities were diagnosed according to malocclusion classification: sagittal (Class-II or III) and vertical (open, normal or deep bite) and facial symmetry. Masseter samples were obtained during mandibular osteotomies, frozen and sectioned for fiber-type immunohistochemistry. Fiber cross-sectional areas (CSA) and mean percent occupancies (MPO) were measured with image-analysis software. Total RNA was isolated from remaining muscle for TaqMan® quantitative RT-PCR. Kendall tau Rank correlation coefficients (r) were determined and tested for significance (p-value).
Results: ATP2A2 expression correlated positively with type-I and type-hybrid and negatively with type-IIA fiber values. Negative correlation with type-IIA MPO was highly significant (r=-0.46; p=0.004). Significant ATP2A2 associations in Class-II subjects were positive with type-I CSA (r=0.36; p=0.04) and negative with type-IIA MPO (r=-0.59; p=0.001). Correlations for Class-III subjects were typically negative and not significant. No significance was found among facial symmetry comparisons, but correlations tended to be negative and lower for asymmetry subjects. Association of ATP2A2 expression with type-I CSA was notably different between asymmetry subjects of Class-II (r= 0.40) and Class-III (r= -0.33) sagittal groups.
Conclusions: ATP2A2 correlations indicate that this calcium channel protein is essential for type-I fiber function, but not type-IIA in masseter muscle from Class-II subjects, suggesting a functional influence on malocclusions. ATP2A2 does not appear to function differentially in fiber types that influence the development of facial asymmetry or Class-III malocclusion.