Thyroid hormone induces ossification and terminal maturation in a preserved OA cartilage biomimetic model.

OBJECTIVE: To characterize aspects of triiodothyronine (T3) induced chondrocyte terminal maturation within the molecular osteoarthritis pathophysiology using the previously established T3 human ex vivo osteochondral explant model. DESIGNS: RNA-sequencing was performed on explant cartilage obtained from OA patients (n = 8), that was cultured ex vivo with or without T3 (10 ng/ml), and main findings were validated using RT-qPCR in an independent sample set (n = 22). Enrichment analysis was used for functional clustering and comparisons with available OA patient RNA-sequencing and GWAS datasets were used to establish relevance for OA pathophysiology by linking to OA patient genomic profiles. RESULTS: Besides the upregulation of known hypertrophic genes EPAS1 and ANKH, T3 treatment resulted in differential expression of 247 genes with main pathways linked to extracellular matrix and ossification. CCDC80, CDON, ANKH and ATOH8 were among the genes found to consistently mark early, ongoing and terminal maturational OA processes in patients. Furthermore, among the 37 OA risk genes that were significantly affected in cartilage by T3 were COL12A1, TNC, SPARC and PAPPA. CONCLUSIONS: RNA-sequencing results show that metabolic activation and recuperation of growth plate morphology are induced by T3 in OA chondrocytes, indicating terminal maturation is accelerated. The molecular mechanisms involved in hypertrophy were linked to all stages of OA pathophysiology and will be used to validate disease models for drug testing.

Complement component C1q is produced by isolated articular chondrocytes.

OBJECTIVE: Inflammation and innate immune responses may contribute to development and progression of Osteoarthritis (OA). Chondrocytes are the sole cell type of the articular cartilage and produce extracellular-matrix molecules. How inflammatory mediators reach chondrocytes is incompletely understood. Previous studies have shown that chondrocytes express mRNA encoding complement proteins such as C1q, suggesting local protein production, which has not been demonstrated conclusively. The aim of this study is to explore C1q production at the protein level by chondrocytes. DESIGN: We analysed protein expression of C1q in freshly isolated and cultured human articular chondrocytes using Western blot, ELISA and flow cytometry. We examined changes in mRNA expression of collagen, MMP-1 and various complement genes upon stimulation with pro-inflammatory cytokines or C1q. mRNA expression of C1 genes was determined in articular mouse chondrocytes. RESULTS: Primary human articular chondrocytes express genes encoding C1q, C1QA, C1QB, C1QC, and secrete C1q to the extracellular medium. Stimulation of chondrocytes with pro-inflammatory cytokines upregulated C1QA, C1QB, C1QC mRNA expression, although this was not confirmed at the protein level. Extracellular C1q bound to the chondrocyte surface dose dependently. In a pilot study, binding of C1q to chondrocytes resulted in changes in the expression of collagens with a decrease in collagen type 2 and an increase in type 10. Mouse articular chondrocytes also expressed C1QA, C1QB, C1QC, C1R and C1S at the mRNA level. CONCLUSIONS: C1q protein can be expressed and secreted by human articular chondrocytes and is able to bind to chondrocytes influencing the relative collagen expression.

A mobile app for postoperative wound care after arthroplasty: Ease of use and perceived usefulness.

BACKGROUND: Early postoperative discharge after joint arthroplasty may lead to decreased wound monitoring. A mobile woundcare app with an integrated algorithm to detect complications may lead to improved monitoring and earlier treatment of complications. In this study, the ease of use and perceived usefulness of such a mobile app was investigated. OBJECTIVE: Primary objective was to investigate the ease of use and perceived usefulness of using a woundcare app. Secondary objectives were the number of alerts created, the amount of days the app was actually used and patient-reported wound infection. METHODS: Patients that received a joint arthroplasty were enrolled in a prospective cohort study. During 30 postoperative days, patients scored their surgical wound by daily answering of questions in the app. An inbuilt algorithm advised patients to contact their treating physician if needed. On day 15 and day 30, additional questionnaires in the app investigated ease of use and perceived usefulness. RESULTS: Sixty-nine patients were included. Median age was 68 years. Forty-one patients (59.4%) used the app until day 30. Mean grade for ease of use (on a Likert-scale of 1-5) were 4.2 on day 15 and 4.2 on day 30; grades for perceived usefulness were 4.1 on day 15 and 4.0 on day 30. Out of 1317 days of app use, an alert was sent to patients on 29 days (2.2%). Concordance between patient-reported outcome and physician-reported outcome was 80%. CONCLUSIONS: Introduction of a woundcare app with an alert communication on possible wound problems resulted in a high perceived usefulness and ease of use. Future studies will focus on validation of the algorithm and the association between postoperative wound leakage and the incidence of prosthetic joint infection.