ArticleOpen biology2019
Osteocyte TSC1 promotes sclerostin secretion to restrain osteogenesis in mice.
Article in Open biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Region- and Compartment-Specific Elevation of Bone Mass in Mice Following Tsc1 Deletion in 8-kb Dmp1-Cre-Expressing Cells.Calcified tissue international · 2026Article
- Loss of Tsc1 in Osterix-expressing cells leads to greater bone mass and strength in mice.Bone · 2026Article
- Sclerostin's role in bone-muscle crosstalk and osteoporosis pathogenesis.Osteoporosis and sarcopenia · 2025Review
- Sirt1: An Increasingly Interesting Molecule with a Potential Role in Bone Metabolism and Osteoporosis.Biomolecules · 2024Review
- Off-target activity of the 8 kb Dmp1-Cre results in the deletion of Tsc1 gene in mouse intestinal mesenchyme.Transgenic research · 2023Article
- The link between bone-derived factors osteocalcin, fibroblast growth factor 23, sclerostin, lipocalin 2 and tumor bone metastasis.Frontiers in endocrinology · 2023Review
- Heterotopic Ossification: Clinical Features, Basic Researches, and Mechanical Stimulations.Frontiers in cell and developmental biology · 2022Review
- Neuronal Induction of Bone-Fat Imbalance through Osteocyte Neuropeptide Y.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Review
- Role of TSC1 in physiology and diseases.Molecular and cellular biochemistry · 2021Review
- Endocrine role of bone in the regulation of energy metabolism.Bone research · 2021Review
- The mTORC1 complex in pre-osteoblasts regulates whole-body energy metabolism independently of osteocalcin.Bone research · 2021Article
- New Advances in Osteocyte Mechanotransduction.Current osteoporosis reports · 2021Review
- The regulation of RANKL by mechanical force.Journal of bone and mineral metabolism · 2021Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteocytes secrete the glycoprotein sclerostin to inhibit bone formation by osteoblasts, but how sclerostin production is regulated in osteocytes remains unclear. Here, we show that tuberous sclerosis complex 1 (TSC1) in osteocytes promotes sclerostin secretion through inhibition of mechanistic target of rapamycin complex 1 (mTORC1) and downregulation of Sirt1. We generated mice with DMP1-Cre-directed Tsc1 gene deletion ( Tsc1 CKO) to constitutively activate mTORC1 in osteocytes. Although osteocyte TSC1 disruption increased RANKL expression and osteoclast formation, it markedly reduced sclerostin production in bone, resulting in severe osteosclerosis with enhanced bone formation in mice. Knockdown of TSC1 activated mTORC1 and decreased sclerostin, while rapamycin inhibited mTORC1 and increased sclerostin mRNA and protein expression levels in MLO-Y4 osteocyte-like cells. Furthermore, mechanical loading activated mTORC1 and prevented sclerostin expression in osteocytes. Mechanistically, TSC1 promotes sclerostin production and prevents osteogenesis through inhibition of mTORC1 and downregulation of Sirt1, a repressor of the sclerostin gene Sost. Our findings reveal a role of TSC1/mTORC1 signalling in the regulation of osteocyte sclerostin secretion and bone formation in response to mechanical loading in vitro. Targeting TSC1 represents a potential strategy to increase osteogenesis and prevent bone loss-related diseases.
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