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Published on: August 25, 2021
Conditional loss of PTEN leads to skeletal abnormalities and lipoma formation
Shu-Chen Hsieh1, Nien-Tsu Chen, Su Hao Lo
1Department of Biochemistry and Molecular Medicine, Center for Tissue Regeneration and Repair, University of California-Davis, Sacramento, California 95817, USA.
Abstract:
To understand the role of tumor suppressor PTEN in cartilage development, we have generated chondrocyte specific PTEN deletion mice using Col2a1Cre and PTEN(loxp/loxp) mice. PTEN mutant mice are viable and fertile, nonetheless, develop kyphosis over time. Histological analyses show mutant vertebrae and intervertebral discs are larger and therefore the spines are longer than in control mice. In addition, the growth plates are thicker, invading trabecular bone areas are deeper, and marrow adipocyte populations are higher in PTEN mutant mice. Furthermore, the growth plates, not normally fused in mouse long bones, are fused in PTEN mutants. Intriguingly, PTEN mice develop lipomas and show abnormal accumulation of fat tissues along spines. Cell tracking assays have confirmed that lipomas and a portion of fat tissues were derived from Col2a1Cre PTEN(loxp/loxp) cells. Further analyses have suggested that the phenotypes of PTEN mutant likely attribute to PTEN's negatively regulating role in PI3K/Akt pathway.
Insights
Tumor suppressor PTEN is crucial for cartilage development. Its deletion in mice leads to spinal deformities, abnormal fat tissue accumulation, and altered growth plate development, impacting skeletal integrity.
Area of Science:
- Skeletal Biology
- Developmental Biology
- Cancer Biology
Background:
- The tumor suppressor PTEN (phosphatase and tensin homolog) plays a critical role in cellular signaling pathways.
- Its involvement in cartilage development and skeletal homeostasis is not fully understood.
- Dysregulation of PTEN is implicated in various cancers and developmental disorders.
Purpose of the Study:
- To investigate the function of PTEN in chondrocyte development and skeletal growth.
- To elucidate the molecular mechanisms underlying PTEN's role in cartilage formation and maintenance.
Main Methods:
- Generation of chondrocyte-specific PTEN deletion mice using Col2a1Cre and PTEN(loxp/loxp) lines.
- Histological and imaging analyses of skeletal structures, including vertebrae, intervertebral discs, and growth plates.
- Cell tracking assays to determine the origin of abnormal tissue formation.
Main Results:
- PTEN mutant mice exhibit kyphosis, enlarged vertebrae and intervertebral discs, and elongated spines.
- Increased growth plate thickness, deeper invading trabecular bone areas, and elevated marrow adipocyte populations were observed.
- PTEN deficiency led to premature fusion of long bone growth plates and the development of lipomas and abnormal spinal fat accumulation, originating from deleted PTEN cells.
- Phenotypes are linked to PTEN's negative regulation of the PI3K/Akt signaling pathway.
Conclusions:
- PTEN is essential for normal cartilage development and skeletal growth.
- Loss of PTEN function in chondrocytes disrupts growth plate integrity and promotes adipogenesis and tumorigenesis.
- PTEN's tumor-suppressive role in the skeleton is mediated through the PI3K/Akt pathway.
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