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Roles of TGF-β in the therapeutic potential of hypoxic mesenchymal stem cells for treating osteoarthritis in a Rabbit
En-Rung Chiang1,2,3, Kun-Hui Chen4,5,6, Hsuan-Hsiao Ma4,5
1Department of Orthopedics and Traumatology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Beitou District, Taipei, Taiwan. rondoo@vghtpe.gov.tw.
Background:
Osteoarthritis (OA) is the most prevalent musculoskeletal disease worldwide. Cell-based therapies have emerged as a promising approach for OA therapy. The therapeutic potential of mesenchymal stem cells (MSCs) has been demonstrated in a wide array of inflammatory diseases. A previous study demonstrated that the injection of the allogeneic MSCs cultured under hypoxia could reduce the progression of osteoarthritis in an anterior cruciate ligament transection (ACLT) model of OA in rabbits. The possible factors involved in the therapeutic effect of hypoxic MSCs in OA were further analyzed in the current study.
Methods:
Using the ACLT model of OA, we investigated gene expression changes in the groups of control, OA, and OA treated by hyaluronic acid (OA + HA), and additionally injected with hypoxic MSCs (OA + HA + MSC) by PCR array.
Results:
Increased expression of TGF-β in the group treated with hypoxic MSCs was observed. Significant higher transcript and protein expressions of TGF-β were also demonstrated in cartilage treated with hypoxic MSCs. We further generated TGF-β-knockout (KO) MSCs and observed notably reduced levels of TGF-β in cartilage treated with hypoxic TGF-β KO MSCs. Immunohistochemical analysis revealed that the group treated with TGF-β KO MSCs exhibited significantly decreased type II collagen (COL II) and increased type X collagen (COL X) as compared to that treated with MSCs without TGF-β-KO.
Conclusions:
Collectively, we suggest hypoxic MSCs might exert therapeutic effects mediated by stimulating TGF-β and subsequently promote and inhibit the expressions of COL II and COL X respectively.
Insights
Hypoxic mesenchymal stem cells (MSCs) show therapeutic potential for osteoarthritis (OA) by stimulating TGF-β. This process influences collagen production, potentially aiding OA treatment.
Area of Science:
- Regenerative Medicine
- Biotechnology
- Orthopedics
Background:
- Osteoarthritis (OA) is a widespread musculoskeletal condition.
- Cell-based therapies, particularly mesenchymal stem cells (MSCs), offer promising OA treatment avenues.
- Previous research indicated that hypoxic MSCs reduce OA progression in rabbit models.
Purpose of the Study:
- To investigate the underlying factors contributing to the therapeutic effects of hypoxic MSCs in OA.
- To analyze gene expression changes in an OA rabbit model treated with hypoxic MSCs.
Main Methods:
- Utilized an anterior cruciate ligament transection (ACLT) rabbit model of OA.
- Compared gene expression using PCR array in control, OA, OA + hyaluronic acid (HA), and OA + HA + hypoxic MSC groups.
- Generated TGF-β knockout (KO) MSCs to assess TGF-β's role.
Main Results:
- Hypoxic MSC treatment increased TGF-β expression in OA cartilage.
- TGF-β knockout MSCs showed reduced TGF-β levels and altered collagen expression (decreased COL II, increased COL X).
- TGF-β appears to mediate the effects of hypoxic MSCs on collagen synthesis.
Conclusions:
- Hypoxic MSCs may exert therapeutic effects in OA by stimulating TGF-β.
- This stimulation influences the expression of Type II Collagen (COL II) and Type X Collagen (COL X).
- TGF-β signaling is a key mechanism in hypoxic MSC-mediated OA therapy.
