Complex Molecular Etiology and Cellular Landscape of Hip Osteoarthritis

Study Overview
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Brief Summary
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The purpose of this study is to cast light on the highly complex etiology and cellular landscape of hip osteoarthritis by utilising single-cell and spatial transcriptomics.

Detailed Description
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The specific objectives of this project are: Using the latest single-cell RNA sequencing (scRNAseq) techniques the investigators aim to A) characterize what kind of cell populations are found in different synovial tissues and blood derived samples of OA patients, B) determine how the cell composition differs between arthritic and corresponding non-arthritic tissues, C) map the transcriptional and regulatory landscape of the cells mentioned in A and B, D) determine what are the key molecular pathways activated in OA. To determine if some of the blood-derived immune cell populations could be used as biomarkers for OA. To map the whole transcriptome of OA and non-arthritic control tissue while keeping the morphological context with spatial transcriptomics technologies. Further differentiation and identification of OA endotypes utilizing the single-cell and spatial data. The project includes a Rheumatoid sub-study where the main objective is to compare arthritic tissue and peripheral blood constituents between OA and rheumatoid arthritis patients to explore the differences in the disease mechanisms.

Official Title
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Studies on the Complex Molecular Etiology and Cellular Landscape of Hip Osteoarthritis

Conditions
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Osteoarthritis, Hip, Rheumatoid Arthritis

Intervention / Treatment
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* Procedure: Total hip arthroplasty


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for the main (OA) study: Cases: Adult patients with osteoarthritis in the hip joint and who are going through an elective total hip arthroplasty. Controls: Non-arthritis adult patients who are going through a trauma-based emergency total hip arthroplasty. ---- Inclusion Criteria for the Rheumatoid sub-study: Adult patients with rheumatoid arthritis in the hip joint and who are going through an elective total hip arthroplasty. ---- Exclusion Criteria: The body mass index must be below 35 Age < 18 or > 74 The OA patients may not have diabetes, rheumatoid arthritis (RA), or metabolic syndrome. For the Rheumatoid sub-study, the exclusion criteria are the same as above except for the RA.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| OA cases<br>Twenty-five adult patients who have hip osteoarthritis. | Procedure: Total hip arthroplasty<br>* Hip joint replacement surgery. Elective for RA and OA cases.<br>|
| RA cases<br>Twenty-five adult patients who have rheumatoid arthritis in the hip joint. | Procedure: Total hip arthroplasty<br>* Hip joint replacement surgery. Elective for RA and OA cases.<br>|
| Non-arthritic controls<br>Fifteen adult patients who go through trauma-based emergency total hip arthroplasty and do not have arthritis. | Procedure: Total hip arthroplasty<br>* Hip joint replacement surgery. Elective for RA and OA cases.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of cell populations in OA | Characterization of cell populations found in different synovial tissues and blood derived samples of OA patients utilising scRNAseq solutions. | Starting during the last quarter of 2022, ending by the last quarter of 2024. | 
| Comparison of cell populations between OA cases and controls | The investigators will determine how the cell composition differs between arthritic and corresponding non-arthritic tissues utilising scRNAseq solutions. | Starting during the last quarter of 2022, ending by the last quarter of 2024. | 
| Cellular landscape in OA | The investigators will map the transcriptional and regulatory landscape of OA at single-cell and tissue (spatial) level. | Starting during the second quarter of 2023, ending by the last quarter of 2024. | 
| Key molecular pathways of OA | The investigators will determine what are the key molecular pathways activated in OA. | Starting during the second quarter of 2023, ending by the last quarter of 2024. | 
| Comparison of disease mechanisms between RA and OA | In the Rheumatoid sub-study the investigators will explore the differences in the disease mechanisms between OA and RA by comparing synovial tissues and peripheral blood sample constituents. | Starting during the last quarter of 2022, ending by the last quarter of 2024. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers for OA | The investigators will investigate if some of the blood-derived immune cell populations could be used as biomarkers for OA. | Starting during the second half of 2023, ending by the first half of 2025. | 
| OA endotypes | The investigators aim to identify and further differentiate OA endotypes by utilizing the single-cell and spatial data. | Starting during the first half of 2024, ending by the second half of 2025. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single-cell RNA sequencing, Spatial transcriptomics, Osteoarthritis, Rheumatoid arthritis