Evaluation of the Multiple Tissue Factors in the Cartilage of Primary and Secondary Rhinoplasty in Cleft Lip and Palate Patients

Cleft lip and palate (CLP) is one of the craniofacial defects. The objective of this study was to identify the differences in appearance between the tissue factors in cartilage of CLP patients after primary and secondary rhinoplasty. Immunohistochemistry was performed with MMP-2, MMP-8, MMP-9, TIMP-2, IL-1α, IL-10, bFGF, and TGFβ1. The quantification of the structures was performed using a semi-quantitative census method. MMP-2, -9, IL-1a, and bFGF demonstrated higher number of positive cells in patients, while the number of MMP-8, IL-1a, -10 and TGFβ1 cells was higher or equal in the control subjects. The only statistically significant difference between CLP-operated patients was found in the TIMP-2 group, where the primary CLP patient group had a higher number of TIMP-2 positive chondrocytes than the secondary CLP patient group (U = 53.5; p = 0.021). The median value of the primary CLP group was ++ number of TIMP-2 positive chondrocytes compared to +++ in the secondary CLP group. No statistically significant difference was found between primary and secondary rhinoplasty patients for other tissue factors. Commonly, the rich expression of different tissue factors suggests a stimulation of higher elasticity in cleft affected cartilage. The statistically significant TIMP-2 elevation in primary operated cartilage indicates an impact of the selective tissue remodeling for hard tissue.publishersversionPeer reviewe

Appearance and distribution of tissue remodellation factors in the hard tissue of patients affected by cleft lip palate

Funding Information: This study was funded by Riga Stradins University, No. 5-1/106/2019 from 12.04.2019, “The elaboration of diagnostic prognostic factor algorithm of facial tissue complex regeneration for cleft patients in longitudinal aspect”. Publisher Copyright: © 2020 Sciendo. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Bone repair after surgical intervention on cleft lip palate (CLP) depends on the coordinated action of multiple tissue regeneration factors. We determined the relative number and appearance of tissue factors: matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), bone morphogenetic protein 2/4 (BMP 2/4), transforming growth factor beta (TGF-ß), Wnt3a protein (Wnt3a), Runt-related transcription factor 2 (Runx2), basic fibroblast growth factor (bFGF) and osteoprotegerin in hard tissue of CLP patients during first time surgical intervention. Fourtythree CLP patients with 24 bone and 36 cartilage samples were involved. Immunohistochemistry was used to assess the levels of tissue factors and the semi-quantitative census method was used for quantification of immunological structures. The increased amount of MMP-2 and bFGF positive cells was detected in the CLP group in cartilage and bone (p < 0.05), compared to the controls. A statistically significant (p = 0.012) increased amount of BMP 2/4 positive cells was found in cartilage of CLP patients, in comparison to the control group. Increased appearance of MMP-2, bFGF in hard tissue of the CLP patients indicates the predominance of tissue degradation. Increased number of BMP2/4 positive chondrocytes suggests improved cartilage growth and better regeneration in CLP patients.publishersversionPeer reviewe

Evaluation of the multiple tissue factors in bone of primary osteoplasty and rhinoplasty in patients affected by cleft lip palate

Clefts of the lip and/or palate (CLP) are visible disruptions of standard facial structure. The aim of our study was to determine a relative number and appearance of the tissue factors in bone of patients with CLP during first time plastic alveolar osteoplasty or rhinoplasty. Immunohistochemistry was performed with matrix metalloproteinase-8 (MMP-8), matrix metalloproteinase9 (MMP-9), osteopontin (OPN), osteocalcin (OC), Runtrelated transcription factor 2 (Runx2), beta-defensin-2 (βdef-2), beta-defensin-3 (βdef-3), interleukin-1 alpha (IL-1α), and interleukin-10 (IL-10). The bone formation was observed by Masson-trichrome (Masson) staining. For the quantification of structures, the semi-quantitative census method was used. Spearman rank order correlation coefficient and Mann-Whitney U test were used for the statistical analysis. A significantly higher number of OPN positive osteocytes was observed in the CLP group when compared to the control group (p=0.002). The number of OC positive osteocytes (p=0.000) and βdef-2 positive osteocytes (p=0.003) was significantly lower in the CLP group in comparison to the control group. Strong, positive correlations between IL-10 and OC (rs=0.608; p=0.002), IL-1α and MMP-9 (rs=0.666; p=0.000), OPN and MMP-8 (rs=0.620; p=0.002) were detected in the CLP group. A tendency for the increased appearance of MMP-8, MMP-9 positive osteocytes of the patients with CLP, suggests elevated tissue remodelling properties. Increased appearance of OPN positive osteocytes in bone of the patients with CLP shows increased bone homeostasis based on seriously decreased mineralization, which may be a possible compensatory reaction to decreased quality of postsurgical bone