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Adipose Tissue-Derived Mesenchymal Stem Cell Inhibits Osteoclast Differentiation through Tumor Necrosis Factor
Kwanghoon Lee1,2, Eunhee Ko1,3, Yongbeom Park4,5,6
1Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Background:
Mesenchymal stem cells (MSCs) have been highlighted as a potent therapeutic option for conditions with excessive osteoclast activity such as systemic and local bone loss in rheumatic disease. In addition to their immunomodulatory functions, MSCs also directly suppress osteoclast differentiation and activation by secreting osteoprotegerin (OPG) and IL-10 but the underlying mechanisms are still to be clarified. Tumor necrosis factor-stimulated gene-6 (TSG-6) is a potent anti-inflammatory molecule that inhibits osteoclast activation and has been shown to mediate MSC's immunomodulatory functions. In this study, we aimed to determine whether adipose tissue-derived MSC (ADMSC) inhibits the differentiation from osteoclast precursors to mature osteoclasts through TSG-6.
Methods:
Human ADMSCs were co-cultured with bone marrow-derived monocyte/macrophage (BMMs) from DBA/1J or B6 mouse in the presence of osteoclastogenic condition (M-CSF 10 ng/mL and RANKL 10 ng/mL). In some co-culture groups, ADMSCs were transfected with siRNA targeting TSG-6 or OPG to determine their role in osteoclastogenesis. Tartrate-resistant acid phosphatase (TRAP) activity in culture supernatant and mRNA expression of osteoclast markers were investigated. TRAP+ multinucleated cells and F-actin ring formation were counted.
Results:
ADMSCs significantly inhibited osteoclast differentiation under osteoclastogenic conditions. Suppression of TSG-6 significantly reversed the inhibition of osteoclast differentiation in a degree similar to that of OPG based on TRAP activity, mRNA expression of osteoclast markers, and numbers of TRAP+ multinucleated cell and F-actin ring formation.
Conclusion:
This study demonstrated that ADMSCs inhibit osteoclast differentiation through TSG-6 under osteoclastogenic conditions.
Insights
Adipose tissue-derived mesenchymal stem cells (ADMSCs) inhibit osteoclast differentiation. This effect is mediated by Tumor necrosis factor-stimulated gene-6 (TSG-6), a key anti-inflammatory molecule.
Area of Science:
- Stem cell biology
- Immunology
- Bone biology
Background:
- Mesenchymal stem cells (MSCs) show therapeutic potential for bone loss conditions driven by excessive osteoclast activity.
- MSCs modulate osteoclastogenesis via factors like osteoprotegerin (OPG) and IL-10, but mechanisms require clarification.
- Tumor necrosis factor-stimulated gene-6 (TSG-6) is an anti-inflammatory molecule that inhibits osteoclast activation and mediates MSC functions.
Purpose of the Study:
- To investigate whether adipose tissue-derived MSCs (ADMSCs) inhibit osteoclast differentiation through TSG-6.
Main Methods:
- Human ADMSCs were co-cultured with mouse bone marrow-derived monocytes/macrophages under osteoclastogenic conditions.
- ADMSCs were transfected with siRNA targeting TSG-6 or OPG to assess their roles.
- Osteoclast differentiation was evaluated by measuring Tartrate-resistant acid phosphatase (TRAP) activity, osteoclast marker gene expression, multinucleated TRAP+ cell counts, and F-actin ring formation.
Main Results:
- ADMSCs significantly inhibited osteoclast differentiation.
- Suppression of TSG-6 reversed this inhibition, comparable to OPG suppression.
- Key osteoclastogenesis markers, including TRAP activity and cell counts, were significantly affected by TSG-6 levels.
Conclusions:
- ADMSCs inhibit osteoclast differentiation via TSG-6 under specific culture conditions.
- TSG-6 plays a crucial role in mediating the anti-osteoclastogenic effects of ADMSCs.
