ArticleThe Journal of clinical investigation2013
Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
177 citing papers in PubMed, 323 citations in OpenAlex.
- Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the Long-Term Odanacatib Fracture Trial.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2015Trial
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Targeting the Ip6k2-Runx2 axis disrupts osteoblast-osteoclast coupling to treat osteoporosis.Nature communications · 2026Article
- Regenerative bone-targeted nanoparticles modulate osteoclast function.Nanoscale horizons · 2026Article
- Beyond resorption: targeting osteoclast fusion and polarization to restore balanced bone remodeling.Frontiers in pharmacology · 2026Review
- Relationship between cathepsin K and extracellular matrix dynamics: a comprehensive review.Frontiers in oncology · 2026Review
- Transcriptomic profiling and RANKL/RANK/OPG-mediated osteoclastogenesis in zebrafish larvae under simulated microgravity conditions.Frontiers in cell and developmental biology · 2026Article
- Beyond resorption-driven coupling: a multi-layered framework for osteoclast-osteoblast communication and its therapeutic consequences.Frontiers in endocrinology · 2026Review
- Article
- Topography-based implants for bone regeneration: Design, biological mechanism, and therapeutics.Materials today. Bio · 2025Review
- Swiprosin-1 Negatively Regulates Osteoclast Differentiation and Bone Resorption via Akt/MAPK/NF-κB Pathway and αvβ3 Integrin-Dependent Signaling.International journal of molecular sciences · 2025Article
- Cathepsin K inhibitors promote osteoclast-osteoblast communication and engagement of osteogenesis.JBMR plus · 2025Article
- Nucleic acid aptamers in orthopedic diseases: promising therapeutic agents for bone disorders.Bone research · 2025Review
- Article
- Sophoraflavanone G Inhibits RANKL-Induced Osteoclastogenesis via MAPK/NF-κB Signaling Pathway.Molecular biotechnology · 2025Article
- Article
- Identification and function of periosteal skeletal stem cells in skeletal development, homeostasis, and disease.Journal of orthopaedic translation · 2025Review
- Beyond resorption: osteoclasts as drivers of bone formation.Cell regeneration (London, England) · 2024Review
- Engineering approaches to manipulate osteoclast behavior for bone regeneration.Materials today. Bio · 2024Review
- The bone nonunion microenvironment: A place where osteogenesis struggles with osteoclastic capacity.Heliyon · 2024Review
117 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cathepsin K (CTSK) is secreted by osteoclasts to degrade collagen and other matrix proteins during bone resorption. Global deletion of Ctsk in mice decreases bone resorption, leading to osteopetrosis, but also increases the bone formation rate (BFR). To understand how Ctsk deletion increases the BFR, we generated osteoclast- and osteoblast-targeted Ctsk knockout mice using floxed Ctsk alleles. Targeted ablation of Ctsk in hematopoietic cells, or specifically in osteoclasts and cells of the monocyte-osteoclast lineage, resulted in increased bone volume and BFR as well as osteoclast and osteoblast numbers. In contrast, targeted deletion of Ctsk in osteoblasts had no effect on bone resorption or BFR, demonstrating that the increased BFR is osteoclast dependent. Deletion of Ctsk in osteoclasts increased their sphingosine kinase 1 (Sphk1) expression. Conditioned media from Ctsk-deficient osteoclasts, which contained elevated levels of sphingosine-1-phosphate (S1P), increased alkaline phosphatase and mineralized nodules in osteoblast cultures. An S1P1,3 receptor antagonist inhibited these responses. Osteoblasts derived from mice with Ctsk-deficient osteoclasts had an increased RANKL/OPG ratio, providing a positive feedback loop that increased the number of osteoclasts. Our data provide genetic evidence that deletion of CTSK in osteoclasts enhances bone formation in vivo by increasing the generation of osteoclast-derived S1P.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.