Evaluation of the presence of MMP-2, TIMP-2, BMP2/4, and TGFβ3 in the facial tissue of children with cleft lip and palate

Abstract

Cleft lip and palate (CLP) is the most common defect affecting the face. The treatment consists of surgical reconstruction of the anatomical structures of the cleft. Part of the surgical treatment is reconstruction of the alveolar bone by means of autogenic bone grafting (osteoplasty). This study aimed to evaluate the levels of expression of extracellular matrix remodeling factors in the facial tissue of children with a complete unilateral (CU) and a complete bilateral (CB) CLP to assess whether the wound healing process is adequate. Twenty-two CLP patients were enrolled in this study. Tissue samples were collected during alveolar osteoplasty for unilateral (n = 12) or bilateral (n = 10) cleft palate, (age range from 6 years 8 months to 12 years 2 months). Control material was obtained in the case of tooth extraction (age range from 6 years 9 months to 14 years 5 months). Immunohistochemistry was used to assess the levels of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), bone morphogenetic proteins 2 and 4 (BMP2/4), and transforming growth factor β3 (TGFβ3). Numbers of positively stained cells were graded semi-quantitatively. Data were analysed using the Kraskel-Wallis rank test and the Bonferroni correction. The total number of MMP2-positive cells was significantly lower in the CBCLP and in the control group than in the CUCLP (p < 0.001 after the Bonferroni correction). The total number of TIMP2-positive cells was significantly higher in the CUCLP than in the CBCLP and in the control group (p < 0.001; p < 0.003 after the Bonferroni correction). The overall number of BMP2/4, TGFβ3-positive cells was significantly higher in the CUCLP than in the CBCLP and in the control group (p < 0.001 after the Bonferroni correction). The decrease of the relative amount of statistically significant BMP2/4, TGFβ3, MMP-2, TIMP-2 containing bone cells in CBCLP patients identifies affected alveolar bone regeneration and remodeling process.

Evaluating the Expression of Candidate Homeobox Genes and Their Role in Local-Site Inflammation in Mucosal Tissue Obtained from Children with Non-Syndromic Cleft Lip and Palate

“…Overexpression of MSX2 (as seen in our study using IHC) caused by sustained TNF-α levels (shown in previous study; Figure 7) [26] leads to NF-κB activation which in turn inhibits the bone morphogenetic protein 2 (BMP2)-induced expression of alkaline phosphatase (ALP) enzyme [73], thereby hindering bone formation. Interestingly, in another study we found a statistically significant decrease in BMP2 and BMP4 expression in bilateral cleft lip and palate tissue [74], which highlights the role of MSX2 in alveolar bone regeneration and the remodeling process. Additionally, interactions between MSX2 and FGF2 in bone formation abnormalities have also been reported [75,76].…”

“…Bone formation and maintenance is a dynamic process that is under the regulatory control of various factors. While we noted previously an increase in FGF/FGFR pathways [40] which promote osteoblast differentiation, a chronic inflammatory state coupled with decrease in BMPs and TGF-β1/3 expression [26,74] usually results in greater bone resorption in cleft patients. This process is further compounded by an increase in the NF-κB expression due to activation of the classical pathway by TNF-α, IL-1β, IL-6, and IL-17 produced by T cells and other cells, all of which have been reported to be elevated in cleft tissue [26].…”

A Comparative Study of the Effects of Platelet-Rich Fibrin, Concentrated Growth Factor and Platelet-Poor Plasma on the Healing of Tooth Extraction Sockets in Rabbits

“…The healing process involves interaction between various cells and growth factors [24]. Therefore, improving the microenvironment of the tooth extraction sockets can promote healing [25] and induce bone tissue regeneration.…”

Orofacial clefts: treatment based on a multidisciplinary approach

“…The palate and face are formed at two different periods, where the primary palate is formed, then the secondary palate. The primary palate gives rise to central structures of the middle face, such as nasal columella, filter, labial tubercle, and premaxilla 11 . The secondary palate originates the palatine processes, which later become the palate itself in the 12th week of intrauterine life.…”