ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2020
FAK Promotes Early Osteoprogenitor Cell Proliferation by Enhancing mTORC1 Signaling.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Activation of the FAK-MAPK/ERK1 pathway promotes intestinal epithelial cell sheet migration during fistula tract repair.Scientific reports · 2026Article
- Regulation of cAMP levels in osteocytes by mechano-sensitive focal adhesion kinase and phosphodiesterase 8A.iScience · 2026Article
- 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
- Role of Oxysterol-Binding Protein Family in Cholesterol Metabolism and Cancer Progression: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- The functional mechanism and clinical significance of miR-3651 in the healing process of Pilon fractures.Journal of orthopaedic surgery and research · 2025Article
- Local abaloparatide administration promotes in situ alveolar bone augmentation via FAK-mediated periosteal osteogenesis.International journal of oral science · 2025Article
- NELL2, a novel osteoinductive factor, regulates osteoblast differentiation and bone homeostasis through fibronectin 1/integrin-mediated FAK/AKT signaling.Bone research · 2025Article
- Nf2-FAK signaling axis is critical for cranial bone ossification and regeneration.Nature communications · 2025Article
- Selective Pyk2 inhibition enhances bone restoration through SCARA5-mediated bone marrow remodeling in ovariectomized mice.Cell communication and signaling : CCS · 2024Article
- Focal adhesion kinase regulates tendon cell mechanoresponse and physiological tendon development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Preliminary study of the homeostatic regulation of osseointegration by nanotube topology.Materials today. Bio · 2024Article
- Inhibition of focal adhesion kinase 2 results in a macrophage polarization shift to M2 which attenuates local and systemic inflammation and reduces heterotopic ossification after polysystem extremity trauma.Frontiers in immunology · 2023Article
- Article
- Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics.Antioxidants (Basel, Switzerland) · 2021Review
- Osteoblast Differentiation and Signaling: Established Concepts and Emerging Topics.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Focal adhesion kinase (FAK) has important functions in bone homeostasis but its role in early osteoprogenitor cells is unknown. We show herein that mice lacking FAK in Dermo1-expressing cells exhibited low bone mass and decreased osteoblast number. Mechanistically, FAK-deficient early osteoprogenitor cells had decreased proliferation and significantly reduced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, a central regulator of cell growth and proliferation. Furthermore, our data showed that the pharmacological inhibition of FAK kinase-dependent function alone was sufficient to decrease the proliferation and compromise the mineralization of early osteoprogenitor cells. In contrast to the Fak deletion in early osteoprogenitor cells, FAK loss in Col3.6 Cre-targeted osteoblasts did not cause bone loss, and Fak deletion in osteoblasts did not affect proliferation, differentiation, and mTORC1 signaling but increased the level of active proline-rich tyrosine kinase 2 (PYK2), which belongs to the same non-receptor tyrosine kinase family as FAK. Importantly, mTORC1 signaling in bone marrow stromal cells (BMSCs) was reduced if FAK kinase was inhibited at the early osteogenic differentiation stage. In contrast, mTORC1 signaling in BMSCs was not affected if FAK kinase was inhibited at a later osteogenic differentiation stage, in which, however, the concomitant inhibition of both FAK kinase and PYK2 kinase reduced mTORC1 signaling. In summary, our data suggest that FAK promotes early osteoprogenitor cell proliferation by enhancing mTORC1 signaling via its kinase-dependent function and the loss of FAK in osteoblasts can be compensated by the upregulated active PYK2. © 2020 American Society for Bone and Mineral Research.
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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.