Molecular pathways involved in knee pain
Research type
Research Study
Full title
Molecular pathways involved in knee pain: an observational study
IRAS ID
275727
Contact name
Ana Valdes
Contact email
Sponsor organisation
The University of Nottingham
Clinicaltrials.gov Identifier
2216668, StepUP OA Versus Arthritis Fund; N/A, NIHR Nottingham Biomedical Research Centre
Duration of Study in the UK
1 years, 6 months, 29 days
Research summary
We collected synovial fluid samples from 71 of individuals with knee osteoarthritis (OA)
OA is a long-term joint disease that worsens with age, causing joint damage. The proteins in the synovial fluid (the liquid inside joints) change as OA gets more severe, but we don’t fully know how aging affects these changes. Understanding how age influences these proteins could help us figure out how OA develops differently in younger versus older people and guide better treatments for different age groups.
This research study aimed to find proteins in the synovial fluid of people with knee OA that are linked to their age and to explore the biological processes these proteins affect. Researchers also wanted to create a model to predict a person’s “biological age” (how old their body seems based on proteins) and see what else might influence this.
The 70 samples collected by our project were jointed to over 1000 samples from Sweden and Oxford all of people with knee OA, and we 7,289 proteins in their synovial fluid with advanced technology. We split the group into two sets (Discovery and Replication) to find and confirm age-related proteins. We used statistical models to study how proteins related to age, accounting for factors like sex and the severity of joint damage seen on X-rays. We also looked at biological pathways (processes in the body) affected by age and built a model to predict biological age based on proteins.
The study found over 300 proteins tied to age, with 279 confirmed in both groups. In the combined group, 1,360 proteins were linked to aging, including some related to stress, cell aging, and damage from oxygen (oxidative stress). Key proteins included Growth differentiation factor 15 (MIC-1), R-spondin-1, and Chordin-like protein 1, with MIC-1 being important in aging and OA due to its role in stress and cell damage. These findings held even when accounting for severe joint damage.
The analysis showed that age affects processes like tissue changes, inflammation, and blood clotting, but these findings weren’t consistent across both groups. We built a model using 209 proteins that accurately predicted a person’s biological age (with a strong correlation of 0.80). Even just using the top 5 proteins gave a good prediction (correlation of 0.69). Many of these proteins were linked to aging regardless of how severe the OA was.
This study shows how aging influences proteins in the joints of people with OA, identifying key proteins and processes that could be targeted for new treatments. The biological age prediction model could help doctors identify patients who seem “older” biologically and hence may benefit from early interventions such as weight loss, education and physiotherapy.
Osteoarthritis (OA) is the most common cause of disability in the elderly population and most individuals suffering from osteoarthritis are managed in the primary care setting. Knee OA is the most common form of arthritis and the most common cause of knee pain in the world.Central Sensitisation (CS) is a marker of pain sensitivity, controlled by the central nervous system (brain and spinal cord) and can appear as widespread pain in multiple areas away from the most painful joint. The presence of CS increases the complexity of the clinical picture and can cause increased pain, disability, emotional distress and poor quality of life. Quantitative Sensory Testing (QST) is a reliable and valid method to assess for the presence of CS and has been found to help with prediction of poor recovery. Establishing the reliability of clinical tests in general and pain testing in particular is essential when these tests are used to help clinicians decide on the most appropriate treatment.
We will recruit 140 individuals with knee pain who, in a single session, will undergo a combination of sample extraction (blood, saliva, urine, synovial fluid and faeces), radiographic examination (x-ray, ultrasound), clinical assessment (use of QST to assess pain sensitivity, strength tests, function and balance tests) and collection of data via a questionnaire booklet (pain, stress, dietary habits, frailty and MSK health). The first 25 out of the 140 participants who will choose to participate in the sub-study will undergo a small QST assessment at the end of their session for reliability and validity purposes.
Based on our findings, future research may use similar clinical assessments to identify people with knee pain who might be helped by using treatment that reduces central sensitisation.
REC name
East Midlands - Derby Research Ethics Committee
REC reference
20/EM/0065
Date of REC Opinion
1 Apr 2020
REC opinion
Further Information Favourable Opinion