The catabolic-to-anabolic shift in the osteoarthritic cartilage after knee joint distraction in dogs occurs after the distraction period

INTRODUCTION: Knee joint distraction (KJD) is a joint-preserving treatment strategy for severe osteoarthritis (OA) that provides long-term clinical and structural improvement [1]. Data from both human trials and animal models indicate clear cartilage regeneration from 6 months and onwards post-KJD [1, 2]. However, recent work showed that during distraction, the balance between catabolic and anabolic indicators is directed towards catabolism, as indicated by collagen type 2 markers [3], proteoglycan (PG) turnover and a catabolic transcription profile [unpublished data]. As such, this study investigates the cartilage directly and 10 weeks after joint distraction in an animal model in order to elucidate the shift from a catabolic to an anabolic cartilage state. METHODS: Knee OA was induced bilaterally in 8 dogs according to the groove model [2]. After 10 weeks of OA induction, the right knee received joint distraction, employing the left knee as an OA control. After 8 weeks of distraction, and after 10 weeks post-KJD, 4 dogs were euthanized. Respectively, macroscopic cartilage degeneration, PG content (Alcian Blue), and PG synthesis ( 35SO4 2- incorporation rate) were assessed [2]. RESULTS & DISCUSSION: Directly after KJD, macroscopic cartilage damage of the right tibial plateau was higher compared to the left OA control (OARSI score: 1.7±0.2 vs 0.6±0.3; p < 0.001). 10 weeks post-KJD this difference persisted (OARSI score: 1.4±0.6 vs 0.6±0.1; p < 0.05). Biochemical analysis of the tibia cartilage directly after KJD revealed a lower PG content (20.1±10.3 mg/g vs 23.7±11.7 mg/g). At 10 weeks post-KJD this difference in PG content was less (24.8±6.8 mg/g vs 25.4±7.8 mg/g). The PG synthesis rate directly after KJD appeared significantly lower vs. OA (1.4±0.6 nmol/h.g vs 5.9±4.4 nmol/h.g; p < 0.001)). However, 10 weeks post-KJD this difference was not detected (3.7±1.2 nmol/h.g vs 2.9±0.8 nmol/h.g), and the synthesis rate in the distracted knee was increased compared to directly after distraction (p < 0.01). CONCLUSIONS: Further in-depth investigation of the material is ongoing; these first results suggest that the shift from a catabolic to an anabolic state occurs within the first weeks after joint distraction, mostly reflected in the biochemical changes. As such, the post-distraction period seems to be essential in identifying key-players that support intrinsic cartilage repair.