ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2015
Thrombospondin-1 regulates bone homeostasis through effects on bone matrix integrity and nitric oxide signaling in osteoclasts.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
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- Decoding cellular communication networks and signaling pathways in bone, skeletal muscle, and bone-muscle crosstalk through spatial transcriptomics in a young male mouse.Bone research · 2026Article
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- TSP-1 interaction with RANK and OPG: implications for bone remodeling and osteolytic bone metastasis.Cell death & disease · 2026Article
- Suppression of distal-less homeobox 3 increased alveolar bone mass in mouse tooth socket by targeting thrombospondin 1.Journal of dental sciences · 2026Article
- The Role of Thrombospondins in Osteoarthritis: from Molecular Mechanisms to Therapeutic Potential.International journal of biological sciences · 2025Review
- Matricellular proteins in immunometabolism and tissue homeostasis.BMB reports · 2024Review
- Unique Spatial Transcriptomic Profiling of the Murine Femoral Fracture Callus: A Preliminary Report.Cells · 2024Article
- Thrombospondins modulate cell function and tissue structure in the skeleton.Seminars in cell & developmental biology · 2024Review
- Exploring the impact of naltrexone on the THBS1/eNOS/NO pathway in osteoporotic bile duct-ligated rats.Scientific reports · 2024Article
- T-cadherin Expressing Cells in the Stromal Vascular Fraction of Human Adipose Tissue: Role in Osteogenesis and Angiogenesis.Stem cells translational medicine · 2022Article
- O-fucosylation of thrombospondin type 1 repeats is essential for ECM remodeling and signaling during bone development.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Cryptotanshinone Suppressed Postmenopausal Osteoporosis by Preventing RANKL-Mediated Osteoclastogenesis against Kidney Injury.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Berbamine inhibits RANKL- and M-CSF-mediated osteoclastogenesis and alleviates ovariectomy-induced bone loss.Frontiers in pharmacology · 2022Article
- The impact of aging and physical training on angiogenesis in the musculoskeletal system.PeerJ · 2022Article
- Article
- The enzymatic hydrolysates from deer sinew promote MC3T3-E1 cell proliferation and extracellular matrix synthesis by regulating multiple functional genes.BMC complementary medicine and therapies · 2021Article
- Platelet TSP-1 controls prostate cancer-induced osteoclast differentiation and bone marrow-derived cell mobilization through TGFβ-1.American journal of clinical and experimental urology · 2021Article
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Authors and funding
8 authors.
Funding
Abstract
Thrombospondin-1 (TSP1), an endogenous antiangiogenic, is a widely expressed secreted ligand with roles in migration, adhesion, and proliferation and is a target for new therapeutics. While TSP1 is present in the bone matrix and several TSP1 receptors play roles in bone biology, the role of TSP1 in bone remodeling has not been fully elucidated. Bone turnover is characterized by coordinated activity of bone-forming osteoblasts (OB) and bone-resorbing osteoclasts (OC). TSP1-/- mice had increased bone mass and increased cortical bone size and thickness compared to wild type (WT). However, despite increased size, TSP1-/- femurs showed less resistance to bending than expected, indicative of diminished bone quality and a bone material defect. Additionally, we found that TSP1 deficiency resulted in decreased OC activity in vivo and reduced OC differentiation. TSP1 was critical during early osteoclastogenesis, and TSP1 deficiency resulted in a substantial overexpression of inducible nitric oxide synthase (iNOS). Importantly, administration of a NOS inhibitor rescued the OC function defects of TSP1-/- mice in vivo. To investigate the role of bone-derived TSP1 in osteoclastogenesis, we found that WT pre-OCs had defective iNOS expression when cultured on TSP1-/- bone compared to WT bone, suggesting that TSP1 in bone plays a critical role in iNOS signaling during OC development. These data implicate a new role for TSP1 in bone homeostasis with roles in maintaining bone matrix integrity and regulating OC formation. It will be critical to monitor bone health of patients administered TSP1-pathway directed therapeutics in clinical use and under development.
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