Single-nucleus multiome profiling reveals osteocyte-centered remodeling of human subchondral bone across osteoarthritis severity

Osteocytes and osteoprogenitors expand with osteoarthritis severity in human medial femoral condyle subchondral bone, with osteocyte SMAD2/3 motif activity rising (rho = 0.70, p = 0.003).

• Why it matters: Osteocytes regulate bone homeostasis but are embedded in mineralized matrix, leaving a gap in single-cell understanding of how subchondral remodeling tracks with OA progression.
• What they did: Subchondral bone from Outerbridge-graded medial femoral condyles was profiled using bulk RNA sequencing (89 knees) and single-nucleus multiome after mechanical nuclear isolation (16 donors), resolving 26 cell states among 61,570 nuclei.
• The result: Osteoprogenitor (p = 0.003) and osteocyte (p = 0.036) fractions increased along an osteogenic continuum, while junction chondrocytes upregulated FN1/FGF/TNFSF11 and inferred FN1 signal to osteocytes rose from 4% to 33% in severe OA.

AI summary of the abstract · may contain errors · not medical advice · read the paper.