Proteoglycan loss and subsequent replenishment in articular cartilage after a mild arthritic insult by IL-1 in mice: Impaired proteoglycan turnover in the recovery phase

Abstract

The reparative responses of articular cartilage after an arthritic insult have not been studied extensively to this day. In the present study, we injected interleukin-1 (IL-1) into knee joints of mice to provoke a mild and transient arthritic insult, and characterized both the catabolic and the subsequent recovery phase. In the catabolic phase, which lasted 2 days after IL-1 injection, proteoglycan (PG) breakdown was profoundly accelerated and PG synthesis was markedly inhibited. Sulfation and polysaccharide synthesis were not affected, yet the number of chondroitin sulfate chains was decreased. The general chondrocyte protein synthesis was not inhibited by IL-1. IL-1 injected every other day for a total of three injections prolonged this catabolic phase and resulted in frank loss of articular cartilage proteoglycans. In the recovery phase, started 3 days after IL-1, PG synthesis was enhanced (1.7 times the normal) and proteoglycans had normal hydrodynamic properties. Remarkably, PG degradation was significantly decreased (approximately 50% of the normal). Zymographic analysis demonstrated enhanced expression of gelatinolytic activities in the extracts of the articular tissues shortly after IL-1 exposure and decreased levels in the recovery phase. We found that the overshoot of PG synthesis and impaired degradation act together to facilitate full cartilage repair 7 days after the last of the three IL-1 injections.

TGF-β/Smad3 Signals Repress Chondrocyte Hypertrophic Differentiation and Are Required for Maintaining Articular Cartilage

“…The reduced proteoglycan production may significantly contribute to osteoarthritis since it may lead to further changes in the components of cartilage matrix and the rate of matrix turnover in Smad3 ex8/ex8 mice. Interestingly, the decreased levels of proteoglycans associated with Smad3 deficiency is similar to that caused by the IL-1 overexpression (van de Loo et al 1994, van de Loo et al 1998). This suggests partial overlapping roles between IL-1 and TGF-β/Smad3 in osteoarthritis initiation and progression.…”

Evaluation of Single-Impact-Induced Cartilage Degeneration by Optical Coherence Tomography

“…Early stages of cartilage degeneration are associated with a loss of proteoglycans [ 41 ], collagen network integrity [ 42 ], and cartilage surface integrity [ 43 ]. In both primary and secondary cartilage degeneration the earliest alterations include surface irregularity formation, erosion, and fissuring and may be consistently detected by OCT. OII as a measure surface irregularity was the only OCT parameter to be significantly affected by impaction, that is, high-energy impact, whereas OHI and OAI were not.…”

T1ρ Magnetic Resonance Imaging for Detection of Early Cartilage Changes in Knees of Asymptomatic Collegiate Female Impact and Nonimpact Athletes

“…13 It has been shown that PG, which provides the compressive stiffness of articular cartilage, is a marker of cartilage health. Because its depletion has been associated with early pathologic changes in articular cartilage and osteoarthritis, 23–25 the ability to measure PG content could permit detection of poor cartilage health, early cartilage damage, or early degenerative changes before these changes were allowed to progress to more advanced joint degeneration.…”