ArticleStem cell research & therapy2025
Subchondral injection of human umbilical cord mesenchymal stem cells ameliorates knee osteoarthritis by inhibiting osteoblast apoptosis and TGF-beta activity.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed.
- Review
- Bakuchiol Ameliorates Glucocorticoid-Induced Osteoporosis by Enhancing Osteoblast Differentiation via Targeting FAT4 to Activate YAP1.Phytotherapy research : PTR · 2026Article
- Enolase 2-mediated lactylation-dependent disruption of the GNL3-MDM2-p53 axis in age-related osteoarthritis.Cellular & molecular biology letters · 2026Article
- Mesenchymal stromal cells therapy for remodeling the joint microenvironment: mechanisms, nanotechnology-enhanced strategies, and translation prospects.Stem cell research & therapy · 2026Review
- Therapeutic effects and potential targets of UC-MSC-Exo in a mouse model of COPD.Scientific reports · 2026Article
- Subchondral Bone Injections for the Treatment of Knee Osteoarthritis.The archives of bone and joint surgery · 2026Article
- Stem cell-based therapies for silicosis: mechanisms, sources, clinical translation, and emerging strategies.Frontiers in immunology · 2026Review
- Needle gauge and length effects on human stem cell viability during injection: a comprehensive review.Frontiers in cell and developmental biology · 2026Review
- Lineage plasticity and signal dysregulation define the cellular trajectory of osteoarthritis progression.Clinical and experimental medicine · 2025Article
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Abstract
backgroundOsteoarthritis (OA) is a common degenerative disease caused by multiple pathological mechanisms wherein subchondral bone malfunction plays a substantial role. Recently, subchondral (SC) injection of orthobiologics has been attracting growing interest albeit the mainstream delivery method of mesenchymal stem cells (MSCs) is through intra-articular (IA). This study investigates the effect of SC injection of human umbilical cord mesenchymal stem cells (UCMSCs) on OA and its possible therapeutic mechanism compared to IA injection.
methodsMale Sprague-Dawley rats with anterior cruciate ligament transection (ACLT) received saline or UCMSC injections via SC or IA. Consecutive injections once a week for three weeks and withdrawal for another four weeks, followed by Radiographical scanning, histopathological, immunohistochemical, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) staining. Cell counting Kit-8 (CCK-8) assay, alkaline phosphatase (ALP), alizarin red staining (ARS), TUNEL, flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed in TNFα-induced MC3T3-E1 cells to illustrate the exact pathogenesis mechanism.
resultsIA and SC UCMSC injections preserved cartilage, synovium, and subchondral bone parameters like trabecular bone volume fraction (BV/TV). SC injection uniquely improved Trabecular separation (Tb.Sp) and Trabecular number (Tb.N). SC and IA injections of UCMSCs demonstrated equivalent efficacy in promoting osteoblastic bone formation and attenuating aberrant angiogenesis of subchondral bone. In addition, we demonstrated that osteoblast apoptosis and Smad2-dependent TGF-beta (TGF-β) are crucial and interactive subchondral bone pathological features in OA. In vivo and vitro studies further revealed that UCMSCs inhibited excessive TGF-β/pSmad2 signaling to regulate aberrant vascularization, osteoblast apoptosis and differentiation imbalance, ultimately maintaining osteochondral homeostasis.
conclusionsThe efficacy of UCMSCs for treating OA rats via SC injection was equivalent to that of IA; and even superior to IA in terms of subchondral bone phenotype via regulating apoptosis and TGF-β/pSmad2 signaling in osteoblasts, suggesting SC injection of UCMSCs as a potential and promising cell therapy for OA treatment.
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