Other genes identified by the network analysis have been previously linked to OA , but have not been studied for their potential as biomarkers / therapeutic targets . For example , Apolipoprotein D ( APOD ) was found to be downregulated in every zone of the OA cartilage . It was also 1 of the 207 mRNAs identified as significantly dysregulated from the meta - analysis and was the top - ranked gene of the MI network . Research has previously implicated APOD as being an important gene in OA pathogenesis . For example , APOD is strongly upregulated by retinoic acid [ 27 ] , which is in turn regulated by ALDH1A2 - an OA risk locus [ 28 ] . In vitro studies have shown APOD to be upregulated upon SOX9 overexpression , a master transcription factor essential for cartilage ECM formation [ 29 ] . Furthermore , a recent study into the identification of knee OA genes shared by both cartilage and synovial tissue proposed that APOD may manage OA through chondrogenesis in articular cartilage and immune regulation in the synovium [ 30 ] . The high ranking of APOD in the MI network makes it an interesting candidate for future studies into OA . In particular , research should investigate its potential as a biomarker / drug target . Fibrillin-1 ( FBN1 ) was another gene that was discovered from analysis of the MI network whose encoded protein was also found to be upregulated in the middle and deep zones of OA cartilage according to the MS data . This is particularly interesting as FBN1 is the causative gene of the inherited connective tissue disorder Marfan syndrome [ 31 ] . Moreover , it was 1 of 300 proteins identified via lectin - affinity chromatography in a previous study investigating the proteome of human OA synovial fluid [ 32 ] . The fact that this gene encodes microfibrils that play a structural role in all connective tissues , and mutations in which are known to cause a disease of the musculoskeletal system , warrants further investigation of its role in OA .