A PTN-Rich MSC Subtype Promotes Cartilage Repair in End-Stage Knee Osteoarthritis
- 1Shandong First Medical University
Abstract
Mesenchymal stem cell (MSC) therapy for end-stage knee osteoarthritis (KOA) shows inconsistent efficacy, and whether MSCs retain cartilage repair capacity in the inflammatory joint remains unclear. Using single-cell RNA sequencing of human Kellgren-Lawrence grade (G ) and (G ) KOA joint tissues and exogenous MSCs, we found that pleiotrophin (PTN) signalling shifts from MSC-chondrocyte crosstalk to chondrocyte-dominated autocrine signalling, with PTN exhaustion and elevated cluster of differentiation 74 (CD74) in G cartilage. We therefore identified and sorted a PTN-rich CD74-low placenta-derived MSC subtype and evaluated it in a murine KOA model and in co-culture with patient-derived chondrocytes. This subtype enhanced cartilage repair, upregulated SOX9, and suppressed MMP13, CD74, IL-6, and IL-1{beta}, potentially through CD74 suppression and reduced NF-{kappa}B signaling. These findings provide a basis for functionally defined, stage-matched cell therapy tailored to the pathological microenvironment of end-stage KOA.
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BibTeX
@misc{wang2026ptnrich,
title = {{A PTN-Rich MSC Subtype Promotes Cartilage Repair in End-Stage Knee Osteoarthritis}},
author = {Z. Wang and L. Yin and F. Zhao and D. Liu and J. Li and J. Chu and Z. Zhou and H. Liu and R. Fan and Z. Yuan and Y. Zhang and L. Liu and G. Yu and M. Sun and B. Shi and J. Han and Y. Zhao},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.764540},
url = {https://www.biorxiv.org/content/10.64898/2026.11.06.764540v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A PTN-Rich MSC Subtype Promotes Cartilage Repair in End-Stage Knee Osteoarthritis
AU - Z. Wang
AU - L. Yin
AU - F. Zhao
AU - D. Liu
AU - J. Li
AU - J. Chu
AU - Z. Zhou
AU - H. Liu
AU - R. Fan
AU - Z. Yuan
AU - Y. Zhang
AU - L. Liu
AU - G. Yu
AU - M. Sun
AU - B. Shi
AU - J. Han
AU - Y. Zhao
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.64898/2026.11.06.764540
UR - https://www.biorxiv.org/content/10.64898/2026.11.06.764540v1
AB - Mesenchymal stem cell (MSC) therapy for end-stage knee osteoarthritis (KOA) shows inconsistent efficacy, and whether MSCs retain cartilage repair capacity in the inflammatory joint remains unclear. Using single-cell RNA sequencing of human Kellgren-Lawrence grade (G ) and (G ) KOA joint tissues and exogenous MSCs, we found that pleiotrophin (PTN) signalling shifts from MSC-chondrocyte crosstalk to chondrocyte-dominated autocrine signalling, with PTN exhaustion and elevated cluster of differentiation 74 (CD74) in G cartilage. We therefore identified and sorted a PTN-rich CD74-low placenta-derived MSC subtype and evaluated it in a murine KOA model and in co-culture with patient-derived chondrocytes. This subtype enhanced cartilage repair, upregulated SOX9, and suppressed MMP13, CD74, IL-6, and IL-1{beta}, potentially through CD74 suppression and reduced NF-{kappa}B signaling. These findings provide a basis for functionally defined, stage-matched cell therapy tailored to the pathological microenvironment of end-stage KOA.
ER -