Roles of Transcriptional Factors Mohawk in Periodontal Ligament

Objectives: Transcriptional factor Mohawk homeobox (Mkx) has been shown to be mainly expressed in tendon tissues and plays an important role in the tissue homeostasis through the regulation of gene expressions such as Col1a1 (Ito et al., PNAS, 2010). Tendons are largely composed of type I collagens and receive mechanical loads such as extension and contraction. Although periodontal ligament (PDL) has many common similarities as well as tendons: PDL is composed of type I collagens largely and receives mechanical loads such as occlusal and/or orthodontic forces, the molecular mechanisms and function of Mkx in PDL have never been clarified. Thus, the aim of this study is to elucidate the expression and function of Mkx in PDL.
Methods: Mkx knockout mice: Venus (an improved green fluorescent protein (GFP) gene ) knockin Mkx deletion mice, which were established previously (Ito et al., PNAS, 2010), were analyzed at 10 weeks, 6 months and 12 months of age. The tissue structure around PDL was examined by immunohistochemistry and histological analysis (H-E and toluidine blue staining). For examination of collagen fibril formation/microstructure and gene expression of PDL, transmission electron microscopy (TEM), qPCR, and microarray analysis were performed.
Results: We found that Mkx is highly expressed in the PDL of the maxillary molars. In Mkx knockout mice, PDL space of the molar furcation area was vertically expanded more than that of WT, which was accompanied by morphological changes of the cells in PDL space. In addition, TEM analysis revealed that collagen fibril of the PDL was abnormally developed in the knockout mice. Finally, we also found that expressions of osteogenic genes were enhanced in PDL of the knockout mice although expressions of PDL-related genes were unchanged.
Conclusions: Our results have disclosed that Mkx has an important role in maintenance of PDL homeostasis.