Elf3 Contributes to Cartilage Degradation in vivo in a Surgical Model of Post-Traumatic Osteoarthritis

• Published in: Scientific reports Vol. 8; no. 1; pp. 6438 - 10
• Main Authors: Wondimu, Elisabeth B., Culley, Kirsty L., Quinn, Justin, Chang, Jun, Dragomir, Cecilia L., Plumb, Darren A., Goldring, Mary B., Otero, Miguel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.04.2018; Nature Publishing Group
• Subjects: 13/106; 13/51; 38; 38/77; 38/90; 631/1647/767/1424; 631/1647/767/2200; 64/110; 692/4023/1670/407; Arthritis; Cartilage diseases; Chondrocytes; Clonal deletion; Collagen; Collagenase; Collagenase 3; Cyclooxygenase-2; Humanities and Social Sciences; IL-1β; Inflammation; Knee; Meniscus; multidisciplinary; Osteoarthritis; Rodents; Science; Science (multidisciplinary); Surgery
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-24695-3

The E-74 like factor 3 (ELF3) is a transcription factor induced by inflammatory factors in various cell types, including chondrocytes. ELF3 levels are elevated in human cartilage from patients with osteoarthritis (OA), and ELF3 contributes to the IL-1β-induced expression of genes encoding Mmp13 , Nos2 , and Ptgs2/Cox2 in chondrocytes in vitro . Here, we investigated the contribution of ELF3 to cartilage degradation in vivo , using a mouse model of OA. To this end, we generated mouse strains with cartilage-specific Elf3 knockout ( Col2 Cre: Elf3 f/f ) and Comp -driven Tet-off-inducible Elf3 overexpression (TRE- Elf3 : Comp -tTA). To evaluate the contribution of ELF3 to OA, we induced OA in 12-week-old Col2 Cre: Elf3 f/f and 6-month-old TRE- Elf3 : Comp -tTA male mice using the destabilization of the medial meniscus (DMM) model. The chondrocyte-specific deletion of Elf3 led to decreased levels of IL-1β- and DMM-induced Mmp13 and Nos2 mRNA in vitro and in vivo , respectively. Histological grading showed attenuation of cartilage loss in Elf3 knockout mice compared to wild type (WT) littermates at 8 and 12 weeks following DMM surgery that correlated with reduced collagenase activity. Accordingly, Elf3 overexpression led to increased cartilage degradation post-surgery compared to WT counterparts. Our results provide evidence that ELF3 is a central contributing factor for cartilage degradation in post-traumatic OA in vivo .