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Updated: May 3, 2026

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Published on: August 23, 2018
TSH inhibits osteoclast differentiation through AMPK signaling pathway
Wenwen Zhang1, Yu Chen1, Yan Wang1
1Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong 250021, China; Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong 250021, China; "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, China; Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong 250021, China.
Purpose:
It is believed that osteoporosis (OP) is associated with hyperthyroidism as a result of the elevation in thyroxine levels. However, patients with subclinical hyperthyroidism, which is characterized by decreased levels of thyroid-stimulating hormone (TSH) alone, are at equal risk of osteoporosis. Research has shown that TSH receptor (TSHR) is expressed on osteoclasts, but whether TSH directly regulates osteoclasts and the underlying mechanisms remain unclear.
Methods:
In this study, we used osteoclast precursor cell conditional TSHR-knockout (TSHR CKO) mouse to study the effects of TSHR knockout on bone metabolism in mice and the changes in osteoclast differentiation in vitro. Transcriptomics was used to identify differentially expressed genes and signaling pathways.
Results:
In vitro, experiments confirmed that TSH inhibited osteoclast differentiation in mouse RAW264.7 monocyte/macrophage cell line and targeted the key signaling pathway AMPK by RNA-seq sequencing. We found TSHR CKO mice exhibited decreased femoral biomechanics and damaged bone microstructure. The serum levels of bone resorption marker were increased, accompanied by an increase in the number of osteoclasts.
Conclusion:
TSH inhibits osteoclast differentiation by activating the AMPK signaling pathway, and exerts an osteoprotective effect. This study will provide guidance for the diagnosis and treatment of osteoporosis. TSH structural analogs or AMPK activators are expected to provide new ideas for the development of drugs to prevent and treat osteoporosis.
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