A reductionist approach to extract robust molecular markers from microarray data series – Isolating markers to track osseointegration

Abstract

Complexities in the full genome expression studies hinder the extraction of tracker genes to analyze the course of biological events. In this study, we demonstrate the applications of supervised machine learning methods to reduce the irrelevance in microarray data series and thereby extract robust molecular markers to track biological processes. The methodology has been illustrated by analyzing whole genome expression studies on bone-implant integration (ossointegration). Being a biological process, osseointegration is known to leave a trail of genetic footprint during the course. In spite of existence of enormous amount of raw data in public repositories, researchers still do not have access to a panel of genes that can definitively track osseointegration. The results from our study revealed panels comprising of matrix metalloproteinases and collagen genes were able to track osseointegration on implant surfaces (MMP9 and COL1A2 on micro-textured; MMP12 and COL6A3 on superimposed nano-textured surfaces) with 100% classification accuracy, specificity and sensitivity. Further, our analysis showed the importance of the progression of the duration in establishment of the mechanical connection at bone-implant surface. The findings from this study are expected to be useful to researchers investigating osseointegration of novel implant materials especially at the early stage. The methodology demonstrated can be easily adapted by scientists in different fields to analyze large databases for other biological processes.

Extensive early mineralization of pre-osteoblasts, inhibition of osteoclastogenesis and faster peri-implant bone healing in osteoporotic rat model: principle effectiveness of bone-specific delivery of Tibolone as evaluated in vitro and in vivo

“…The early and superior mineralization could possibly be attributed to the early upregulation of ALP gene and its enzymatic activity in response to the drug. Relative expression of early osteogenic markers such as ALP, COL1A2, RUNX2, OCN, etc was also found to be stimulated in response to the drug up to day 7, where the potential of COL1A2 to be an early marker of osteogenesis was predicted in a previous publication of the author (Barik et al 2017). The above findings clearly indicate that 3α-OH Tibolone promotes early mineralization and thus points towards a strong pro-osteogenic role of Tibolone.…”

“…At the molecular level, TRAP + cells are also known to express some hallmark genes typical to osteoclasts, like TRAP, CTR, Cathepsin K (CTSK), etc (Hsu et al 1999). While TRAP is an established marker for osteoclast formation as discussed above, MMP9, also being an indicator of activated osteoclasts, may be utilized as the biomarker to detect osteoclast activity (Barik et al 2017). Analysis of qPCR data showed that the drug significantly inhibits osteoclast maturation by affecting all the hallmark genes discussed above.…”

COL3A1, COL6A3, and SERPINH1 Are Related to Glucocorticoid-Induced Osteoporosis Occurrence According to Integrated Bioinformatics Analysis

“…In a previous study on bone and mineral research, COL6A3 was found to have a significant correlation with osteoclast-like cell expression [ 37 ]. Furthermore, Barik et al [ 47 ] demonstrated that COL6A3 expression on superimposed nano-textured surfaces was related to track osseointegration on implant surfaces. A previous study reported that COL6A3 participated in chondrocyte hypertrophic differentiation as well as ECM integrity in cartilage and basement membrane [ 48 ].…”

Enhanced osteogenesis of titanium with nano-Mg(OH)2 film and a mechanism study via whole genome expression analysis

“…Currently, for millions of patients who benefit from orthopedic surgery, titanium (Ti) is one of the most frequently used orthopedic implants [ [1] , [2] , [3] ]. Despite improvements in surgical procedures, postoperative care, and many other perspectives which all aim to speed up healing after bone implantation, insufficient osteointegration followed by aseptic loosening remains the key limiting factor of biomaterials made of Ti [ [4] , [5] , [6] ].…”