ArticleHuman molecular genetics2007
Novel pycnodysostosis mouse model uncovers cathepsin K function as a potential regulator of osteoclast apoptosis and senescence.
Article in Human molecular genetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 116 citations in OpenAlex.
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- Article
- Pycnodysostosis: a case series of eight Saudi patients with cathepsin K gene mutation and a literature review.Frontiers in endocrinology · 2025Review
- Ageing-related bone and immunity changes: insights into the complex interplay between the skeleton and the immune system.Bone research · 2024Review
- Article
- Heparan sulfate selectively inhibits the collagenase activity of cathepsin K.Matrix biology : journal of the International Society for Matrix Biology · 2024Article
- Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging.Aging cell · 2024Review
- Heparan sulfate selectively inhibits the collagenase activity of cathepsin K.bioRxiv : the preprint server for biology · 2024Article
- Mesenchymal stem cells in craniofacial reconstruction: a comprehensive review.Frontiers in molecular biosciences · 2024Review
- Atp6i deficient mouse model uncovers transforming growth factor-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation.International journal of oral science · 2023Article
- Treatment with an inhibitor of matrix metalloproteinase 9 or cathepsin K lengthens embryonic lower jaw bone.Orthodontics & craniofacial research · 2023Article
- Knockout and Double Knockout of Cathepsin K and Mmp9 reveals a novel function of Cathepsin K as a regulator of osteoclast gene expression and bone homeostasis.International journal of biological sciences · 2022Article
- Cathepsin KFrontiers in cell and developmental biology · 2022Review
- Hypoxia-inducible factor-2α mediates senescence-associated intrinsic mechanisms of age-related bone loss.Experimental & molecular medicine · 2021Article
- Runt-related transcription factor 1 is required for murine osteoblast differentiation and bone formation.The Journal of biological chemistry · 2020Article
- Whole-exome sequencing identified a novel variant in an Iranian patient affected by pycnodysostosis.Molecular genetics & genomic medicine · 2020Article
- Article
- C1 Silencing Attenuates Inflammation and Alveolar Bone Resorption in Endodontic Disease.Journal of endodontics · 2019Article
- Macrophage-lineage TRAP+ cells recruit periosteum-derived cells for periosteal osteogenesis and regeneration.The Journal of clinical investigation · 2019Article
- Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Pycnodysostosis is a genetic bone disease featuring the unique bone homeostasis disorders of osteolysis and osteopetrosis in the same organism. The pathomechanism for pycnodysostosis has been largely unknown due to the unavailability of a pycnodysostosis mouse model with all the traits of the disease. We generated cathepsin K(-/-) mouse strains in the 129/Sv and C57BL/6J backgrounds and found that, only in the 129/Sv background, cathepsin K(-/-) mice exhibit many characteristics of the human pycnodysostosis-like phenotype. Our data indicated that 129/Sv cathepsin K(-/-) osteoclasts (OCs) lacked normal apoptosis and senescence and exhibited over-growth both in vitro and in vivo. These abnormalities resulted in an unusually high OC number, which is consistent with a recent case study of human pycnodysostosis. Our results show that cathepsin K function has different effects around the skeleton due to site-specific variations in bone homeostasis, such as phenotypes of osteopetrosis in tibiae and osteolysis in calvariae as a result of cathepsin K mutation. Our data demonstrated that the expression levels of p19, p53 and p21 were significantly reduced in 129/Sv cathepsin K(-/-) OCs and forced expression of cathepsin K in pre-OCs induced premature senescence and increased expression of p19, p53 and p21. This is the first evidence that cathepsin K plays a key role in OC apoptosis and senescence, revealing the importance of OC senescence in bone homeostasis. The finding of this novel cathepsin K function provides insight into the pathomechanism of pycnodysostosis and may provide new drug targets for diseases involved in OC-related abnormal bone homeostasis.
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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.