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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Thy1 is a positive regulator of osteoblast differentiation and modulates bone homeostasis in obese mice
Ananta Paine1, Collynn F Woeller2, Hengwei Zhang3,4
1Division of Allergy, Immunology, and Rheumatology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA.
Abstract:
Thy1 (CD90), a glycosylated, glycophosphatidylinositol-anchored membrane protein highly expressed by subsets of mesenchymal stem cells and fibroblasts, inhibits adipogenesis. The role of Thy1 on bone structure and function has been poorly studied and represents a major knowledge gap. Therefore, we analyzed the long bones of wild-type (WT) and Thy1 knockout (KO) mice with micro-computed tomography (micro-CT) and histomorphometry to compare changes in bone architecture and overall bone structure. micro-CT analysis of long bones revealed Thy1 KO and WT mice fed a high-fat diet demonstrated bone structural parameters at 4 mo that differed significantly between WT and KO mice. A significant reduction in trabecular bone volume was noted in Thy1 KO mice. The most prominent differences were observed in trabecular bone volume ratio and trabecular bone connectivity density. Consistent with micro-CT measurements, histomorphometric analysis also showed decreased bone volume in the obese Thy1 KO mice compared to obese WT mice. In vitro assays revealed that osteogenic conditions increased Thy1 expression during OB differentiation and absence of Thy1 attenuated osteoblastogenesis. Together, these findings support the concept that Thy1 serves as a major mechanistic link to regulate bone formation and negatively regulate adipogenesis.-Paine, A., Woeller, C. F., Zhang, H., Garcia-Hernandez, M. L., Huertas, N., Xing, L., Phipps, R. P., Ritchlin, C. T. Thy1 is a positive regulator of osteoblast differentiation and modulates bone homeostasis in obese mice.
Insights
Thy1 (CD90) is crucial for bone health, promoting osteoblast differentiation. Its absence in mice led to reduced bone volume and altered structure, especially in obese individuals, highlighting its role in bone homeostasis.
Area of Science:
- Bone biology
- Stem cell research
- Metabolic bone disease
Background:
- Thy1 (CD90) is a membrane protein known to inhibit adipogenesis.
- Its specific role in bone structure and function remains largely uncharacterized.
- Understanding Thy1's impact on bone is critical for addressing bone-related disorders.
Purpose of the Study:
- To investigate the role of Thy1 in regulating bone structure and homeostasis.
- To compare bone architecture in wild-type (WT) and Thy1 knockout (KO) mice, particularly under high-fat diet conditions.
- To elucidate the in vitro effects of Thy1 on osteoblast differentiation.
Main Methods:
- Analysis of long bones from WT and Thy1 KO mice using micro-computed tomography (micro-CT) and histomorphometry.
- Assessment of bone structural parameters, including trabecular bone volume and connectivity density.
- In vitro osteogenic differentiation assays to evaluate Thy1 expression and function.
Main Results:
- Thy1 KO mice exhibited significantly reduced trabecular bone volume and altered bone structure compared to WT mice, especially when fed a high-fat diet.
- Histomorphometry confirmed decreased bone volume in obese Thy1 KO mice.
- In vitro studies showed increased Thy1 expression during osteoblast differentiation, with its absence attenuating osteoblastogenesis.
Conclusions:
- Thy1 is a positive regulator of osteoblast differentiation and plays a significant role in maintaining bone homeostasis.
- Thy1 deficiency negatively impacts bone structure and volume, particularly in the context of obesity.
- These findings identify Thy1 as a key mediator linking bone formation and adipogenesis regulation.
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