Defining the extracellular matrix in non-cartilage soft-tissues in osteoarthritis: a systematic review

Listen to Simon and Amy discuss the paper 'Defining the extracellular matrix in non-cartilage soft-tissues in osteoarthritis: a systematic review' published in the December 2024 issue of Bone & Joint Research.

Click here to read the paper.

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Transcript

[00:00:00] Welcome back to another episode of AI Talks with Bone & Joint from the publishers of Bone & Joint Research. Today, we're discussing the paper 'Defining the extracellular matrix in non-cartilage soft-tissues in osteoarthritis: a systematic review' published in December 2024 by I G. A. Raza, S J. B. Snelling and J Y. Mimpen. I am Simon and I am joined by my co-host, Amy. 

Hello, everyone. Simon, this paper delves into the extracellular matrix, or ECM, in osteoarthritis, specifically examining non-cartilage soft-tissues. Could you start by explaining the motivation behind this research? 

Certainly, Amy. The authors aim to address the significant gap in our understanding of osteoarthritis, which is the most prevalent joint disease globally. Affecting over 500 million people, most osteoarthritis research concentrates on cartilage, but other soft-tissues such as ligaments, meniscus, synovium and tendons are also impacted. 

These tissues are abundant in the ECM, [00:01:00] which plays a crucial role in tissue mechanics and cell behavior. However, the ECM in non-cartilage tissues has been poorly characterized in osteoarthritis. This study aims to consolidate existing data on the composition and architecture of ECM in these tissues. 

Let's delve into the methods they employed. The researchers conducted a systematic review based on a protocol registered on the PROSPERO database. They conducted searches in the MEDLINE, EMBASE, and Scopus databases for relevant studies, searching for studies describing ECM components and architectural features in non-cartilage soft joint tissues. 

They included both human and animal studies, ensuring the animal models had valid control groups. They also performed a bias analysis to evaluate the quality of the included studies.

The results were extensive. They included 161 studies covering a wide range of tissues such as capsule, ligaments, meniscus, skeletal muscle, synovium and tendon in both humans and animals. Along with fat pad and [00:02:00] intervertebral disc in humans only. 

An interesting finding was that while some ECM changes, such as calcification and loss of collagen fibre organization, were extensively studied, most other ECM features were investigated by only a few papers for each tissue. This emphasises how underexplored this area is. 

Indeed. Another key point is the need for validation from human studies when using animal models. While results from animal experiments generally agreed with human studies, there were some contradictions. This highlights the importance of choosing the right model. 

It's evident that changes in ECM composition and architecture occur throughout non-cartilage soft-tissues in osteoarthritic joints. However, due to the low number of studies and lack of healthy comparator groups, many of these changes remain poorly defined. 

The authors also noted that most of the human studies included in the review lacked well defined control groups. Furthermore, the roles of ECM components like proteoglycans, collagens and [00:03:00] glycosaminoglycans varied across the studies.

Absolutely. Regarding ECM architecture, some studies showed a decrease in collagen fibre diameter and organization in osteoarthritis tissues, but the results on viscoelastic properties were conflicting. 

Let's touch on some tissues that were less examined. The joint capsule and fat pad were very poorly defined in the context of osteoarthritis, possibly reflecting their perceived lower importance in the disease.

And when comparing findings from human osteoarthritis to animal models, the authors observed some consistent patterns, like increased calcification and disrupted collagen organization. However, some observations contradicted the human data, particularly in meniscus studies. 

It's also important to consider the gender disparity in osteoarthritis research. Most human osteoarthritis studies involve more female subjects due to higher prevalence in women, while many animal studies are conducted on male animals. 

Indeed, this [00:04:00] gender bias in preclinical research can affect study outcomes and interpretations. Fortunately, sex-specific differences are increasingly being addressed in osteoarthritis research, which is vital for developing accurate models and treatments.

In summary, this systematic review provides a consolidated view of ECM changes in non-cartilage soft-tissues in osteoarthritis. While it brings together a lot of information, it also highlights significant gaps and inconsistencies in current research. To truly understand osteoarthritis, the entire joint needs to be considered, not just the cartilage.

Future research should focus on the detailed study of all joint tissues and their ECM features across different stages of osteoarthritis. 

For our listeners interested in further details, we highly recommend reading the full paper. It marks a significant step towards a more comprehensive understanding of osteoarthritis.

Thank you for tuning in to AI Talks with Bone & Joint. Until next time.