Intravascular Ultrasound (IVUS): A Potential Arthroscopic Tool for Quantitative Assessment of Articular Cartilage

Conventional ultrasound examination of the articular cartilage performed externally on the body surface around the joint has limited accuracy due to the inadequacy in frequency used. In contrast to this, minimally invasive arthroscopy-based ultrasound with adequately high frequency may be a better alternative to assess the cartilage. Up to date, no special ultrasound transducer for imaging the cartilage in arthroscopic use has been designed. In this study, we introduced the intravascular ultrasound (IVUS) for this purpose. An IVUS system with a catheter-based probe (Ø ≈ 1mm) was used to measure the thickness and surface acoustical reflection of the bovine patellar articular cartilage in vitro before and after degeneration induced by enzyme treatments. Similar measurement was performed using another high frequency ultrasound system (Vevo) with a probe of much larger size and the results were compared between the two systems. The thickness measured using IVUS was highly correlated (r = 0.985, p < 0.001) with that obtained by Vevo. Thickness and surface reflection amplitude measured using IVUS on the enzymatically digested articular cartilage showed changes similar to those obtained by Vevo, which were expectedly consistent with previous investigations. IVUS can be potentially used for the quantitative assessment of articular cartilage, with its ready-to-use arthroscopic feature

Isothiocyanates are detected in human synovial fluid following broccoli consumption and can affect the tissues of the knee joint

Osteoarthritis is a major cause of disability and there is no current pharmaceutical treatment which can prevent the disease or slow its progression. Dietary advice or supplementation is clearly an attractive option since it has low toxicity and ease of implementation on a population level. We have previously demonstrated that sulforaphane, a dietary isothiocyanate derived from its glucosinolate precursor which is found in broccoli, can prevent cartilage destruction in cells, in in vitro and in vivo models of osteoarthritis. As the next phase of this research, we enrolled 40 patients with knee osteoarthritis undergoing total knee replacement into a proof-of-principle trial. Patients were randomised to either a low or high glucosinolate diet for 14 days prior to surgery. We detected ITCs in the synovial fluid of the high glucosinolate group, but not the low glucosinolate group. This was mirrored by an increase in ITCs and specifically sulforaphane in the plasma. Proteomic analysis of synovial fluid showed significantly distinct profiles between groups with 125 differentially expressed proteins. The functional consequence of this diet will now be tested in a clinical trial

Identifying chondroprotective diet-derived bioactives and investigating their synergism

Osteoarthritis (OA) is a multifactorial disease and nutrition is a modifiable factor that may contribute to disease onset or progression. A detailed understanding of mechanisms through which diet-derived bioactive molecules function and interact in OA is needed. We profiled 96 diet-derived, mainly plant-based bioactives using an in vitro model in chondrocytes, selecting four candidates for further study. We aimed to determine synergistic interactions between bioactives that affected the expression of key genes in OA. Selected bioactives, sulforaphane, apigenin, isoliquiritigenin and luteolin, inhibited one or more interleukin-1-induced metalloproteinases implicated in OA (MMP1, MMP13, ADAMTS4, ADAMTS5). Isoliquiritigenin and luteolin showed reactive oxygen species scavenging activity in chondrocytes whereas sulforaphane had no effect and apigenin showed only a weak trend. Sulforaphane inhibited the IL-1/NFκB and Wnt3a/TCF/Lef pathways and increased TGFβ/Smad2/3 and BMP6/Smad1/5/8 signalling. Apigenin showed potent inhibition of the IL-1/NFκB and TGFβ/Smad2/3 pathways, whereas luteolin showed only weak inhibition of the IL-1/NFκB pathway. All four bioactives inhibited cytokine-induced aggrecan loss from cartilage tissue explants. The combination of sulforaphane and isoliquiritigenin was synergistic for inhibiting MMP13 gene expression in chondrocytes. We conclude that dietary-derived bioactives may be important modulators of cartilage homeostasis and synergistic relationships between bioactives may have an anti-inflammatory and chondroprotective role