Abstract
Osteoarthritis (OA) is the most common arthritis and its hallmark is degradation of articular cartilage by proteolytic enzymes leading to loss of joint function. It is challenging to monitor the status of cartilage in vivo and this study explores the use of autofluorescence lifetime (AFL) measurements to provide a label-free optical readout of cartilage degradation that could enable earlier detection and evaluation of potential therapies. We previously reported that treatment of ex vivo porcine cartilage with proteolytic enzymes resulted in decreased AFL. Here we report changes in AFL of ex vivo mouse knee joints, porcine metacarpophalangeal joints, normal human metatarsophalangeal articular tissue and human OA tibial plateau tissues measured with or without treatment using a compact single-point time resolved spectrofluorometer. Our data show that proteolytically damaged areas in porcine metacarpophalangeal joints present a reduced AFL and that inducing aggrecanases in mouse and human joints also significantly reduces AFL. Further, human cartilage from OA patients presents a significantly lower AFL compared to normal human cartilage. Our data suggest that AFL can detect areas of cartilage erosion and may potentially be utilised as a minimally-invasive diagnostic readout for early stage OA in combination with arthroscopy devices.
Highlights
Osteoarthritis (OA) is the most common joint disease, affecting around 10% of men and 18% of women over 60 years of age[1]
We are not able to conclude if this decrease is due to aggrecan depletion or collagen degradation, the data suggest that proteolytic damage caused by matrix metalloproteinases (MMP)-1 can be detected by autofluorescence lifetime (AFL) in mouse joint cartilage
The only way to detect these molecular events in cartilage tissue ex vivo is physical dissection of the cartilage followed by histological analysis
Summary
Osteoarthritis (OA) is the most common joint disease, affecting around 10% of men and 18% of women over 60 years of age[1]. ADAMTS5 null mice were protected from cartilage degradation in an experimental OA model[7] This suggests that aggrecan removal is a crucial early event in OA progression and a minimally invasive tool that could report aggrecan depletion would be of great interest for early diagnosis of OA. The application of fluorescence lifetime readouts to cartilage autofluorescence was reported in 200413 and subsequent work on ex vivo engineered cartilage tissue has shown the potential for autofluorescence lifetime (AFL) measurements to provide label-free readouts of cartilage degradation following specific treatments with collagenase, chondroitinase-ABC and ribose[14]. We have previously reported that both the degradation of collagen and the removal of aggrecans from natural ex vivo cartilage are associated with a decrease in AFL of cartilage tissue following treatment with bacterial collagenase, human MMP-1 and, trypsin; and aggrecanase induction by retinoic acid treatment of live cartilage[15]. This study focused on (1) how chemically-induced aggrecan depletion affects the AFL of intact murine, porcine and human cartilage; (2) whether AFL measurements can report local enzymatically-induced damage in the articular cartilage surface; (3) determining if AFL measurements can be used to detect natural erosion in human tibial plateau cartilage
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