Journal: bioRxiv

Article Title: Circulating pre-osteoclasts are primed for osteoclast fate and synovial tissue homing in psoriatic arthritis

doi: 10.64898/2026.03.21.713366

Figure Lengend Snippet: A) Schematic of workflow for radiolabelling imaging studies. 2 healthy volunteers and 3 patients with active PsA were recruited. 168ml of blood was taken and clinical grade PBMCs isolated using erythrocyte sedimentation and iso-osmotic plasma-percoll gradients. Monocytes were selected using magnetic positive selection using CliniMACS CD14 pos beads. Purified monocytes were labelled with a target of 1000MBq of Tc 99m– HMPAO, and autologously reinfused. Initial dynamic planar imaging was performed over the lungs and upper abdomen to explore their reinfusion kinetics. Following this, sequential planar images of participants knees, feet/ankles, and hands/wrists performed at 45-minutes, 2-, 4-, and 24-hours. Donors with PsA underwent an ultrasound-guided synovial biopsy after their 24-hour imaging timepoint. B, C) Images of knees, feet/ankles, and hands/wrists from healthy donors (B) and PsA donors (C). Images are composites, representing the geometric mean of counts measured from both anterior and posterior scanners over the 20 minutes of image capture. An exception is that of the hands/wrists which are from posterior scanner only. Right side of image indicated with reference source. Images are normalised to injected activity. Red arrows indicate accumulation of activity inflamed joints. For MONOQUANT1 donor, uptake seen in both knees, ankles, wrists, and right (R) metacarpophalangeal (MCP) 2, and 3, and left (L) MCP 3 joints. For MONOQUANT2 donor, uptake seen in R knee, R metatarsophalangeal (MTP) 1, L MTP 1-2, R wrist, R MCP 1-2, L MCP 1-2 joints. For MONOQUANT4 donor, uptake seen in both knees, ankles, R MTP 1, both wrists, and R MCP1 joints. D) Distribution of radioactivity to bilateral wrist joints over time for all donors in counts per pixel per MBq above background radiation, normalised to first time point of imaging. E) Correlation of radiolabelling findings with musculoskeletal ultrasound. Top panels indicate inflamed joints of note from PsA donor (MONOQUANT1) who underwent musculoskeletal ultrasound assessment prior to synovial biopsy. To right are relevant ultrasound images of regions. Effusions indicated with *, white arrows indicate errors of synovial hyperplasia. Red arrows indicate accumulation of activity inflamed joints.

Article Snippet: After PBMC isolation as described above, monocyte enrichment was carried out using positive selection with the CD14 MicroBead kit (Miltenyi, 130-050-201) as per the manufacturer’s instructions.

Techniques: Imaging, Isolation, Sedimentation, Clinical Proteomics, Selection, Purification, Injection, Activity Assay, Radioactivity

Journal: bioRxiv

Article Title: Circulating pre-osteoclasts are primed for osteoclast fate and synovial tissue homing in psoriatic arthritis

doi: 10.64898/2026.03.21.713366

Figure Lengend Snippet: A) Schematic to develop gating strategy for preOC cells. B) Output of HyperFinder-derived gating strategy. Top panels show the suggested gating strategy with bottom panels showing the effect of the above gate on the UMAP visualisation. Monocytes are gated on using CD88 and CD89. DCSTAMP pos cells are next selected, already showing strong enrichment for the preOC tail. CCR3 pos CCR9 pos cells are then gated on, before CD14 pos ITGA7 pos ITGAV pos cells are selected. C) Inclusion and workflow of additional control – cutaneous psoriasis without arthritis (PsC) donors. D) Representative HyperFinder-derived gating strategies of healthy (top panels), PsC (middle panels), and PsA (lower panels) of suspension mass cytometry acquired blood PBMCs. E) Quantification of preOC population shown as proportion of total CD45 pos cells per donor. PsC cohort includes one donor highlighted in red who developed active PsA with inflammatory back pain and dactylitis. P-values were calculated utilising Mann-Witney U, **p-value<0.01, ***p-value<0.001. F) UMAP visualisation of blood MPs cells with heatmap overlay of enrichment for “synovial tissue homing” scores from Moon et al , 2023.

Article Snippet: After PBMC isolation as described above, monocyte enrichment was carried out using positive selection with the CD14 MicroBead kit (Miltenyi, 130-050-201) as per the manufacturer’s instructions.

Techniques: Derivative Assay, Control, Suspension, Mass Cytometry