An optical probe for detecting chondrocyte apoptosis in response to mechanical injury

Yihui Huang,Amirhossein Hakamivala,Jinglei Wu,Yi Hong,Liping Tang,Joseph Borrelli,Jun Zhou

doi:10.1038/s41598-017-10653-y

Abstract

Cartilage injury induced by acute excessive contact stress is common and mostly affects young adult. Although early detection of cartilage injury may prevent serious and lifelong arthritic complications, early detection and treatment is not possible due to the lack of a reliable detection method. Since chondrocyte injury and subsequent cell death are the early signs of cartilage injury, it is likely that cartilage cell apoptosis can be used to predict the extent of injury. To test this hypothesis, a near infrared probe was fabricated to have high affinity to apoptotic cells. In vitro tests show that this apoptosis probe has low toxicity, high specificity, and high affinity to apoptotic cells. In addition, there is a positive relationship between apoptotic cell numbers and fluorescence intensities. Using a mouse xiphoid injury model, we found significant accumulation of the apoptosis probes at the injured xiphoid cartilage site. There was also a positive correlation between probe accumulation and the number of apoptotic chondrocytes within the injured xiphoid cartilage, which was confirmed by TUNEL assay. The results support that the apoptosis probes may serve as a powerful tool to monitor the extent of mechanical force-induced cartilage injury in vivo.

Highlights

It is estimated that more than 27 million adults in the United States suffer from osteoarthritis, approximately 12% of these individuals have a type of osteoarthritis that develops due to a mechanical force-induced cartilage injury[1, 2]
There is a loss of resident cells in the articular cartilage, which results in impaired extracellular matrix and potentially in the development of cartilage injury[27, 28]
Previous studies have demonstrated that the H1-targeting peptide can bind H1 that is exposed on the surface of apoptotic cells[39, 40]

Summary

Introduction

It is estimated that more than 27 million adults in the United States suffer from osteoarthritis, approximately 12% of these individuals have a type of osteoarthritis that develops due to a mechanical force-induced cartilage injury ( called as post-traumatic osteoarthritis)[1, 2]. Magnetic resonance images provide a three-dimensional view of cartilage that may elucidate cartilage irregularities[8] Since these structural changes can only be appreciated during the intermediate or late stages of cartilage injury, these conventional methods cannot be used to detect early changes within the injured cartilage. A folate-targeted NIR probe has been used in vivo to image rheumatoid arthritis in mice; namely, this is because the synovial membrane in mice with rheumatoid arthritis has been shown to accumulate large numbers of activated macrophages, which have upregulated folate receptors[21] These probes have been developed to detect inflammatory responses and products associated with inflammatory arthritis. We believe that the detection of apoptotic chondrocytes soon after cartilage injury can be used to determine the extent of the cartilage injury that can possibly lead to early treatment and prevention

Methods

Results

Conclusion