Osteoarthristis (OA) has been associated with many genes and yet the genetic basis for this disease has never formally been established. Recent realization that epigenetic changes could be the underlying pathological mechanisms has helped to explain many complex multifactorial diseases with no clear genetic cause. We therefore asked whether epigenetics could also play a role in OA. We have previously shown that the DNA epigenetic modification, specifically the hydroxymethylation on cytosine (5hmC), undergoes a fivefold increase on OA-associated genes which are activated at OA onset. In this study, we further uncovered a set of 5hmC-mediated gene targets and their mechanistic link to OA progression. We surgically induced OA on 4 to 6 months old Tet1−/− mice (Tet1tm1.1Jae, the Jackson laboratory) and wild-type littermates by performing destabilization of the medial meniscus (DMM) surgery. Joints were collected for histological assessment through blinded grading with the OARSI scoring system. Human articular chondrocytes were harvested from OA cartilage samples obtained during total knee arthroplasty or from grossly normal cartilage pieces obtained during notchplasty or debridement from patients undergoing anterior cruciate ligament (ACL) reconstruction with no history of OA symptoms, under approved Human subjects Institutional Review Board protocols. Bioinformatic analyses of RNA-sequencing and CCGG sequencing (reduced representation 5hmC profiling) were performed to identify TET1 target genes associated with OA progression. Several measurements were used to assess the effect of TET1 ablation on the phenotype of mouse cartilage tissue and human chondrocytes including, histological evaluation, and quantitative bone assessment by micro-CT imaging and multiplex cytokine analyses in the serum of mice in vivo (mouse 39-plex assay) and in the supernatant of human chondrocyte cultures (human 62-plex assay).Introduction and Objective
Materials and Methods
There is little published evidence regarding cannabis or cannabinoid use among orthopedic patients, yet there is increasing public attention on its possible role in treating various medical conditions including pain. California passed legislation legalizing cannabis for medical treatment in 2003 and recreational use in 2018. All patients undergoing total joint arthroplasty (TJA) at our institution are screened preoperatively with a urine toxicology (UTox) screen. Though a positive test for other substances triggers surgery cancellation, a positive screen for cannabis and/or opiates does not impact whether surgery is performed. We sought to quantify the prevalence of cannabinoid and opioid use among patients with chronic pain from end-stage hip and knee osteoarthritis who underwent arthroplasty at our institution in 2012 and 2017. Institutional Review Board approval was obtained. A retrospective chart review was performed for all patients with severe arthritis who underwent total hip and knee arthroplasty (THA and TKA) at our institution during the calendar years 2012 and 2017. Patients were excluded if TJA was performed for acute trauma or if no pre-operative UTox screen was obtained. The UTox screen was used to determine preoperative cannabis and opioid use. Chi-squared testing was performed, and significance was defined as p<=0.05.Introduction
Methods
