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Updated: Nov 19, 2025

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Parathyroid hormone type 1 receptor regulates osteosarcoma K7M2 Cell growth by interacting with angiotensinogen
Shenglong Li1, Fei Liu1, Yi Pei1
1Department of Bone and Soft Tissue Tumor Surgery, Liaoning Cancer Hospital & Institute, Cancer Hospital of China Medical University, Shenyang, China.
Abstract:
This study aimed to determine the interactions between parathyroid hormone type 1 receptor (PTHR1) and angiotensinogen (AGT) and the effects of these agents on osteosarcoma (OS). We constructed a stably transfected mouse OS K7M2 cell line (shPTHR1- K7M2) using shRNA and knocked down AGT in these cells using siRNA-AGT. The transfection efficiency and expression of AGT, chemokine C-C motif receptor 3 (CCR3), and chemokine (C-C motif) ligand 9 (CCL9) were determined using real-time quantitative PCR. Cell viability and colony formation were assessed using Cell Counting Kit-8 and crystal violet staining, respectively. Cell apoptosis and cycle phases were assessed by flow cytometry, and cell migration and invasion were evaluated using Transwell assays. Interference with PTHR1 upregulated the expression of AGT and CCR3, and downregulated that of CCL9, which was further downregulated by AGT knockdown. Cell viability, migration, invasion and colony formation were significantly decreased, while cell apoptosis was significantly increased in shPTHR1-K7M2, compared with those in K7M2 cells (P < .05 for all). However, AGT knockdown further inhibited cell viability after 72 h of culture but promoted cell migration and invasion. PTHR1 interference decreased and increased the numbers of cells in the G0/G1 and G2/M phases, respectively, compared with those in K7M2 cells. Angiotensinogen knockdown increased the number of cells in the G0/G1 phase compared with that in the shPTHR1-K7M2 cells. Therefore, PTHR1 affects cell viability, apoptosis, migration, invasion and colony formation, possibly by regulating AGT/CCL9 in OS cells.
Insights
Parathyroid hormone type 1 receptor (PTHR1) interference impacts osteosarcoma (OS) cell growth and spread. PTHR1 affects OS cell viability, apoptosis, and migration, potentially by regulating angiotensinogen (AGT) and chemokine ligand 9 (CCL9).
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Osteosarcoma (OS) is a primary bone malignancy with limited treatment options.
- The parathyroid hormone type 1 receptor (PTHR1) and angiotensinogen (AGT) pathways are implicated in various cellular processes, but their interplay in OS is not fully understood.
Purpose of the Study:
- To investigate the interaction between PTHR1 and AGT in osteosarcoma cells.
- To elucidate the effects of modulating PTHR1 and AGT on OS cell behavior, including viability, apoptosis, migration, invasion, and cell cycle progression.
Main Methods:
- A stably transfected mouse OS cell line (shPTHR1-K7M2) was generated using shRNA to knock down PTHR1.
- siRNA was used to knock down AGT expression.
- Real-time quantitative PCR, Cell Counting Kit-8, crystal violet staining, flow cytometry, and Transwell assays were employed to assess gene expression and cellular functions.
Main Results:
- PTHR1 interference upregulated AGT and CCR3 expression while downregulating CCL9.
- Knockdown of PTHR1 significantly decreased OS cell viability, migration, invasion, and colony formation, and increased apoptosis.
- AGT knockdown further inhibited cell viability but promoted migration and invasion in PTHR1-interfered cells.
Conclusions:
- PTHR1 plays a crucial role in regulating osteosarcoma cell proliferation, apoptosis, migration, and invasion.
- The observed effects of PTHR1 interference are potentially mediated through the regulation of the AGT/CCL9 signaling axis.
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