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Published on: January 20, 2018
Tumor Proteins D52 and D54 Have Opposite Effects on the Terminal Differentiation of Chondrocytes
Chihiro Ito1, Yoshiki Mukudai1, Masakatsu Itose1,2
1Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan.
Abstract:
The tumor protein D (TPD) family consists of four members, TPD52, TPD53, TPD54, and TPD55. The physiological roles of these genes in normal tissues, including epidermal and mesenchymal tissues, have rarely been reported. Herein, we examined the expression of TPD52 and TPD54 genes in cartilage in vivo and in vitro and investigated their involvement in the proliferation and differentiation of chondrocytes in vitro. TPD52 and TPD54 were uniformly expressed in articular cartilage and trabecular bone and were scarcely expressed in the epiphyseal growth plate. In MC3T3E-1 cells, the expressions of TPD52 and TPD54 were increased in a differentiation-dependent manner. In contrast, their expressions were decreased in ATDC5 cells. In ATDC5 cells, overexpression of TPD52 decreased alkaline phosphatase (ALPase) activity, while knock-down of TPD52 showed little effect. In contrast, overexpression of TPD54 enhanced ALPase activity, Ca2+ deposition, and the expressions of type X collagen and ALPase genes, while knock-down of TPD54 reduced them. The results revealed that TPD52 inhibits and that TPD54 promotes the terminal differentiation of a chondrocyte cell line. As such, we report for the first time the important roles of TPD52 and TPD54, which work oppositely, in the terminal differentiation of chondrocytes during endochondral ossification.
Insights
Tumor protein D52 (TPD52) inhibits chondrocyte differentiation, while TPD54 promotes it. These opposing roles of TPD52 and TPD54 are crucial for endochondral ossification.
Area of Science:
- Biochemistry
- Cell Biology
- Orthopedics
Background:
- The tumor protein D (TPD) family, including TPD52, TPD53, TPD54, and TPD55, has poorly understood physiological roles in normal tissues.
- Limited information exists regarding the function of TPD genes in epidermal and mesenchymal tissues, particularly in cartilage development.
Purpose of the Study:
- To investigate the expression of TPD52 and TPD54 genes in cartilage.
- To elucidate the roles of TPD52 and TPD54 in chondrocyte proliferation and differentiation in vitro.
- To understand the opposing functions of TPD52 and TPD54 in chondrocyte terminal differentiation during endochondral ossification.
Main Methods:
- Examined TPD52 and TPD54 gene expression in articular cartilage and trabecular bone in vivo.
- Analyzed gene expression in chondrocyte cell lines (MC3T3E-1 and ATDC5) in vitro.
- Utilized gene overexpression and knockdown techniques in ATDC5 cells to assess effects on alkaline phosphatase (ALPase) activity, calcium deposition, and gene expression.
Main Results:
- TPD52 and TPD54 were widely expressed in articular cartilage and bone, but not in the epiphyseal growth plate.
- TPD52 and TPD54 expression increased with differentiation in MC3T3E-1 cells but decreased in ATDC5 cells.
- TPD52 overexpression inhibited ALPase activity, while TPD54 overexpression enhanced ALPase activity, calcium deposition, and expression of type X collagen and ALPase genes in ATDC5 cells.
Conclusions:
- TPD52 acts as an inhibitor of chondrocyte terminal differentiation.
- TPD54 promotes chondrocyte terminal differentiation, evidenced by increased ALPase activity and matrix mineralization.
- TPD52 and TPD54 play opposing, critical roles in regulating chondrocyte differentiation during endochondral ossification.
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