Title:Human Umbilical Cord Mesenchymal Stem Cells Alleviate Rat Knee Osteoarthritis
via Activating Wnt/ β-catenin Signaling Pathway
Volume: 19
Issue: 2
Author(s): Yue Zhou, Yingjie Zhao, Yujiao Wu, Jingyu Chen, Huaxun Wu, Wei Wei*Shangxue Yan*
Affiliation:
- Institute of Clinical Pharmacology, Anhui Medical University, Hefei, 230032, China
- Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, 230032, China
- Anti-inflammatory Immune
Drug Collaborative Innovation Center, Hefei, 230032, Anhui Province, China
- Rheumatoid Arthritis Research Center,
Anhui Medical University, Hefei, 230032, China
- Institute of Clinical Pharmacology, Anhui Medical University, Hefei, 230032, China
- Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, 230032, China
- Anti-inflammatory Immune
Drug Collaborative Innovation Center, Hefei, 230032, Anhui Province, China
- Rheumatoid Arthritis Research Center,
Anhui Medical University, Hefei, 230032, China
Keywords:
Osteoarthritis, chondrocytes, human umbilical cord mesenchymal stem cells, GAGs, Wnt/β-catenin signaling pathway, glycosaminoglycan.
Abstract:
Background: Osteoarthritis (OA) is a chronic disease characterized by joint cartilage degeneration,
destruction, and osteogenic hyperplasia. Human umbilical cord mesenchymal stem cells (hUCMSCs)
have attracted increasing research interest due to their high clonogenic, proliferative, and migratory
potential, as well as their improved secretion of relevant chondrogenic factors. This study evaluated the
therapeutic potential and underlying mechanism of hUC-MSCs in alleviating pathological symptoms of
OA.
Methods: For the in vivo study, OA rats were established by the Hulth method to observe the therapeutic
effect of intra-articular injection of hUC-MSCs. X-ray tests, gross observations, and histological and immunohistochemical
assessments were conducted in rats. Levels of interleukin-1 beta (IL-1β), IL-6, matrix
metalloproteinase-13 (MMP-13), and tissue inhibitor matrix metalloproteinase-1 in rats’ synovial fluid
were measured using enzyme-linked immunosorbent assay kits. For the in vitro study, hUC-MSCs and
chondrocytes were cultured to explore the effect and underlying mechanisms of hUC-MSCs on OA.
Apoptosis, proliferation, and glycosaminoglycan (GAG) were measured in the chondrocytes. The relative
expression of aggrecan, COL-2, and SOX-9 mRNA was quantified by real-time polymerase chain reaction.
Expressions of Wnt/β-catenin signaling molecules were measured by Western blot.
Results: We found that intra-articular injection of hUC-MSCs reduced the combined score, increased the
expression of collagen II, and decreased the expression of MMP-13, IL-1β, and IL-6 in rat knee joints.
Additionally, hUC-MSCs increased the content of GAGs, inhibited chondrocyte apoptosis, and promoted
chondrocyte proliferation. The expression of aggrecan, COL-2, and SOX-9 mRNA in chondrocytes was
promoted by hUC-MSCs via activation of the Wnt/β-catenin signaling pathway.
Conclusion: Overall, this study demonstrated that hUC-MSCs induce the secretion of some cytokines via
the paracrine function to activate the Wnt/β-catenin signaling pathway to reduce the pathological condition
of OA and maintain the proper expression of cytokines and extracellular matrix proteins.
