Osteoarthritis (OA) is a multifactorial joint disease mainly affecting articular cartilage (AC) with a relevant biomechanical component. During endochondral ossification growth plate (GP) chondrocytes arrange in columns. GPs do not ossify in skeletally mature rodents. In neonatal mice, an altered joint loading induces GP chondrocyte disorganization. We aimed to study whether experimental OA involves GP disorganization in adult mice and to assess if it may have additional detrimental effects on AC damage. Knee OA was induced by destabilization of the medial meniscus (DMM) in wild-type (WT) adult mice, and in Tamoxifen-inducible Ellis-van-Creveld syndrome protein (Evc) knockouts (EvccKO), used as a model of GP disorganization due to Hedgehog signalling disruption. Chondrocyte column arrangement was assessed in the tibial GP and expressed as Column Index (CI). Both DMM-operated WT mice and non-operated-EvccKO showed a decreased CI, indicating GP chondrocyte column disarrangement, although in the latter, it was not associated to AC damage. The most severe GP chondrocyte disorganization occurred in DMM-EvccKO mice, in comparison to the other groups. However, this altered GP structure in DMM-EvccKO mice did not exacerbate AC damage. Further studies are needed to confirm the lack of interference of GP alterations on the analysis of AC employing OA mice.

Inflammatory activity in rheumatoid arthritis may alter the regulation of muscle mass leading to a secondary sarcopenia, commonly termed rheumatoid cachexia (RC). We characterized alterations to muscle structure and various pro-inflammatory, catabolic and regenerative markers in an animal model of RC. Antigen induced arthritis (AiA) was performed in 20 male adult rabbits. AiA animals exhibited significantly less weight gain, a markedly elevated serum C-reactive protein (CRP), lighter muscles with shorter cross-sectional diameter and increased myonuclei when compared to controls. Atrogin-1 and MuRF-1 were up-regulated alongside an increase in IL-1β, active NF-κB and a higher ratio of phosphorylated to inactive p38 MAPK. CCL-2 and TNF levels were reduced and IL-6 was unchanged between groups. We observed decreased pSTAT3, unchanged pSTAT1 and Myf5, but increased Pax7, MyoD and myogenin. AiA rabbits had a reduction in myostatin from gastrocnemii and synovium with a congruent decrease in serum myostatin compared to controls. Chronic arthritis induced an RC-like secondary sarcopenia with increased muscle protein breakdown. Elevated IL-1β may trigger proteolysis via elevated NF-κB and p38 MAPK signaling with a compensatory anabolic response suggested by myonuclear expansion, increased Pax7, MyoD and myogenin, reduced pSTAT3 as well as reduced serum, synovial and muscular myostatin.

Active inflammation could be associated with lipid accumulation within macrophages of CA rabbits. JAK inhibition induced lipid release through RCT activation, providing a plausible explanation for the effect of tofacitinib on the lipid profile of RA patients.