isolation-monocyte-macrophage-lineage-cells-from-rat-bones-secondary

Isolation of Monocyte-Macrophage Lineage Cells from Rat Bones by Secondary Adherence Method

With a decrease of bone mineral density, bones are more likely to fracture, thus negatively affecting a patient's quality of life. The growth and ...

Zhejiang Chinese Medical University

Osteoclast cell increase is a major risk factor for osteoporosis and degenerative bone and joint diseases. At present, RANKL and M-CSF are commonly used to induce osteoclastogenesis. Thioacetamide (TAA) can lead to many types of liver and kidney damage, but less attention has been paid to the association of TAA with bone damage. In this work, we investigated the effects of TAA on the osteoclastogenesis and differentiation of bone marrow macrophages (BMMs).

Thioacetamide promotes osteoclast transformation of bone marrow macrophages by influencing PI3K/AKT pathways.

There is an increasing incidence of destructive bone disease caused by osteoclast proliferation. This is characterized by reduced bone mass and imbalance of bone homeostasis. Icariin (ICA), a flavonoid compound isolated from , has anti‑osteoporosis activity and inhibits the formation of osteoclasts and bone resorption. The purpose of the present study was to investigate the protective effect of ICA on osteoclastic differentiation induced by thioacetamide (TAA) and its possible mechanism in Sprague Dawley (SD) rats. In the present study, SD rats were intraperitoneally injected with TAA (300 mg/kg) for the bone loss model, treated with ICA (600 mg/kg, intragastric gavage) in the ICA group and TAA+ICA group for treatment of bone loss for 6 weeks. Indexes associated with bone metabolism, such as alkaline phosphatase, N‑terminal telopeptide of type‑I collagen (NTX‑I), calcium (Ca), phosphorus (P) and magnesium (Mg) in the serum, were detected. Osteoclast differentiation of femoral tissues was detected by hematoxylin and eosin and tartrate‑resistant acid phosphatase staining. The femoral bone mass was evaluated using a three‑point bending test and micro computed tomography. Western blotting was used to detect the expression levels of osteoclast‑related proteins in each group. In the rats treated with TAA, the serum concentrations of Ca, P and Mg were decreased, the serum concentration of NTX‑I was increased, osteoclast differentiation of the femur was increased, femur bone stress and bone mass were decreased and the bone loss and osteoclast formation were reduced after ICA treatment. In addition, ICA inhibited the protein expression of receptor activator of nuclear factor κ‑Β ligand (RANKL), receptor activator of nuclear factor κ‑B (RANK), p38, ERK, c‑Fos and nuclear factor of activated T cells 1 (NFATc1) in the femur of rats treated with TAA. The results suggested that ICA may inhibit osteoclast differentiation by downregulating the RANKL‑p38/ERK‑NFAT signaling pathway and prevent TAA‑induced bone loss. The results are helpful to understand the mechanism of osteoclast differentiation induced by TAA, as well as the antiresorptive activity and molecular mechanism of ICA, and to provide new ideas for the treatment of osteolytic diseases.

Icariin attenuates thioacetamide‑induced bone loss via the RANKL‑p38/ERK‑NFAT signaling pathway.

Thioacetamide (TAA) is widely used in the production of drugs, pesticides and dyeing auxiliaries. Moreover, it is a chemical that can cause liver damage and cancer. TAA has recently been identified to cause bone damage in animal models. However, the type of bone damage that TAA causes and its potential pathogenic mechanisms remain unclear. The toxic effects of TAA on the femurs of New Zealand white rabbits and the underlying toxicity mechanism were investigated in this study. Serum samples, the heart, liver, kidney and femurs were collected from rabbits after intraperitoneal injection of TAA for 5 months (100 and 200 mg/kg). The New Zealand white rabbits treated with TAA showed significant weight loss and femoral shortening. The activities of total bilirubin, total bile acid and gamma-glutamyl transpeptidase in the serum were increased following treatment with TAA. In addition, thinned cortical bone and significantly decreased trabecular thickness of TAA-treated rabbits was observed, which was accompanied by significantly decreased mineral density of the cortical and trabecular bone. Moreover, there was a significant decrease in modulus of elasticity and maximum load on bone stress in TAA-treated rabbits. The western blotting results showed that the expression of phosphorylated (p)-p38 and p-ERK in femur tissues of rabbits were increased after TAA administration. Collectively, these results suggested that TAA may lead to femoral damage in rabbits by activating the p38/ERK signaling pathway.

Toxic effects of thioacetamide-induced femoral damage in New Zealand white rabbits by activating the p38/ERK signaling pathway.

Thioacetamide (TAA) is used in various fields, such as synthetic drugs, organic chemical synthesis, and materials chemistry. TAA is mainly used to establish animal liver injury models and other organ damage models to explore their mechanisms for helping patients with liver disease. Liver damage can lead to abnormal expression of some enzymes in the serum, so we detected the appropriate enzyme levels in the serum of SD rats to verify the damage of TAA to the liver. More importantly, TAA caused bone damage is barely understood. Therefore, our research aims to establish a rat model reflecting the acute bone damage injury caused by TAA.

Article	Year
Thioacetamide promotes osteoclast transformation of bone marrow macrophages by influencing PI3K/AKT pathways. Journal of orthopaedic surgery and research\| PubMed ID: 35093114	2022
Icariin attenuates thioacetamide‑induced bone loss via the RANKL‑p38/ERK‑NFAT signaling pathway. Molecular medicine reports\| PubMed ID: 35169865	2022
Toxic effects of thioacetamide-induced femoral damage in New Zealand white rabbits by activating the p38/ERK signaling pathway. Physiological research\| PubMed ID: 35275703	2022
Acute bone damage through liver-bone axis induced by thioacetamide in rats. BMC pharmacology & toxicology\| PubMed ID: 35526079	2022

Xiaoli Jin

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