Chondrocyte ‐Specific RUNX2 Overexpression Accelerates Post‐traumatic Osteoarthritis Progression in Adult Mice

ABSTRACTRUNX2 is a transcription factor critical for chondrocyte maturation and normal endochondral bone formation. It promotes the expression of factors catabolic to the cartilage extracellular matrix and is upregulated in human osteoarthritic cartilage and in murine articular cartilage following joint injury. To date, in vivo studies of RUNX2 overexpression in cartilage have been limited to forced expression in osteochondroprogenitor cells preventing investigation into the effects of chondrocyte ‐specific RUNX2 overexpression in postnatal articular cartilage. Here, we used theRosa26Runx2 allele in combination with the inducibleCol2a1CreERT2 transgene or the inducibleAcanCreERT2 knock ‐in allele to achieve chondrocyte‐specific RUNX2 overexpression (OE) during embryonic development or in the articular cartilage of adult mice, respectively. RUNX2 OE was induced at embryonic day 13.5 (E13.5) for all developmental studies. Histology and in situ hybridization analyses suggest an e arly onset of chondrocyte hypertrophy and accelerated terminal maturation in the limbs of the RUNX2 OE embryos compared to control embryos. For all postnatal studies, RUNX2 OE was induced at 2 months of age. Surprisingly, no histopathological signs of cartilage degeneration were observed even 6 mont hs following induction of RUNX2 OE. Using the meniscal/ligamentous injury (MLI), a surgical model of knee joint destabilization and meniscal injury, however, we found that RUNX2 OE accelerates the prog...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: ORIGINAL ARTICLE Source Type: research