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NFATC1 and NFATC2 expression patterns in human osteochondromas
Yuanyuan Wang1,2, Jiangdong Ren3, Guojin Hou4
1Department of Stomatology, Xuanwu Hospital Capital Medical University, Beijing, China.
Background:
Our previous study in genetic mouse models found that NFATc1 and NFATc2 suppress osteochondroma formation from entheseal progenitors. However, it remains unclear whether NFAT signaling is also involved in human osteochondromagenesis. As the first step in addressing this question, the current study aimed to determine the expression patterns of NFATC1 and NFATC2 in human osteochondroma samples.
Methods:
Immunohistochemistry (IHC) was used to examine and analyze NFATC1 and NFATC2 expression in human osteochondroma samples. The human periosteum was used to map the expression of NFATC1 under physiological conditions by IHC. Furthermore, human periosteal progenitors were isolated and identified from the periosteal tissues of bone fracture healing patients. The expression of NFATC1 in human periosteal progenitors was characterized by Western blotting compared to human bone marrow stromal cells (BMSC).
Results:
The IHC results showed that the expression of NFATC1 was undetectable in most human osteochondromas cells, and only a small proportion of osteochondroma cells, especially clonally grown chondrocytes, showed positive staining of NFATC1. NFATC2 expression was also undetectable in most chondrocytes in human osteochondromas. The mouse and human periosteum showed a comparable ratio of NFATC1 positive cells (9.56 ± 0.80% vs 11.04 ± 2.05%, P = 0.3101). Furthermore, Western blotting analysis revealed that NFATC1 expression was highly enriched in human periosteal progenitors compared to BMSC.
Conclusions:
NFATC1 and NFATC2 are undetectable in most human osteochondroma chondrocytes. The expression pattern of NFATC1 in human osteochondromas and the normal periosteum suggests that NFAT signaling could be suppressed during human osteochondromagenesis.
Insights
Nuclear Factor of Activated T-cells (NFAT) signaling, specifically NFATc1 and NFATc2, appears suppressed in human osteochondromas. This contrasts with mouse models, suggesting a different role in human osteochondroma development.
Area of Science:
- Molecular biology
- Cell biology
- Oncology
- Orthopedics
Background:
- Previous studies in mouse models indicated that NFATc1 and NFATc2 inhibit osteochondroma formation.
- The role of NFAT signaling in human osteochondroma development remains largely unknown.
- Osteochondromas are benign bone tumors often affecting adolescents and young adults.
Purpose of the Study:
- To investigate the expression patterns of NFATc1 and NFATc2 in human osteochondroma samples.
- To determine if NFAT signaling is involved in human osteochondrogenesis.
- To compare NFATc1 expression in human osteochondromas with normal human periosteum and progenitors.
Main Methods:
- Immunohistochemistry (IHC) was employed to analyze NFATc1 and NFATc2 expression in human osteochondromas.
- IHC was used to map NFATc1 expression in the human periosteum.
- Western blotting characterized NFATc1 expression in human periosteal progenitors compared to bone marrow stromal cells (BMSC).
Main Results:
- NFATc1 and NFATc2 expression was largely undetectable in human osteochondroma chondrocytes.
- A small subset of osteochondroma cells, particularly clonally grown chondrocytes, showed positive NFATc1 staining.
- NFATc1 expression in the human periosteum was comparable to mouse periosteum, and highly enriched in periosteal progenitors versus BMSC.
Conclusions:
- NFATc1 and NFATc2 are generally absent in human osteochondroma chondrocytes.
- The observed expression pattern suggests NFAT signaling may be suppressed during human osteochondroma development.
- Further research is needed to elucidate the precise role of NFAT signaling in human osteochondrogenesis.
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