ArticleEndocrinology2019
Glucocorticoid-Induced Bone Fragility Is Prevented in Female Mice by Blocking Pyk2/Anoikis Signaling.
Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- MLM3 and MLM5 head and neck cancer models promote age-dependent musculoskeletal deterioration in mice.Scientific reports · 2025Article
- 7-Hydroxyflavone Mitigates OsteoporosisCurrent topics in medicinal chemistry · 2025Article
- Research progress of PYK2 in digestive system diseases.Frontiers in immunology · 2025Review
- Generation of BT-Amide, a Bone-Targeted Pyk2 Inhibitor, EffectiveJournal of medicinal chemistry · 2024Article
- Pharmacologic or genetic interference with atrogene signaling protects against glucocorticoid-induced musculoskeletal and cardiac disease.JCI insight · 2024Article
- Protein kinase G2 activation restores Wnt signaling and bone mass in glucocorticoid-induced osteoporosis in mice.JCI insight · 2024Article
- Mitochondria from osteolineage cells regulate myeloid cell-mediated bone resorption.Nature communications · 2024Article
- Article
- Reversal of the diabetic bone signature with anabolic therapies in mice.Bone research · 2023Article
- Pathogenic mechanisms of glucocorticoid-induced osteoporosis.Cytokine & growth factor reviews · 2023Review
- Osteoporosis in Patients With Respiratory Diseases.Frontiers in physiology · 2022Review
- The osteocyte as a signaling cell.Physiological reviews · 2022Review
- Bad to the Bone: The Effects of Therapeutic Glucocorticoids on Osteoblasts and Osteocytes.Frontiers in endocrinology · 2022Review
- Osteoclasts protect bone blood vessels against senescence through the angiogenin/plexin-B2 axis.Nature communications · 2021Article
- Article
- Pyk2 deficiency enhances bone mass during midpalatal suture expansion.Orthodontics & craniofacial research · 2020Article
- MicroRNA-29a Counteracts Glucocorticoid Induction of Bone Loss through Repressing TNFSF13b Modulation of Osteoclastogenesis.International journal of molecular sciences · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Excess of glucocorticoids (GCs) is a leading cause of bone fragility, and therapeutic targets are sorely needed. We report that genetic deletion or pharmacological inhibition of proline-rich tyrosine kinase 2 (Pyk2) prevents GC-induced bone loss by overriding GC effects of detachment-induced bone cell apoptosis (anoikis). In wild-type or vehicle-treated mice, GCs either prevented osteoclast apoptosis or promoted osteoblast/osteocyte apoptosis. In contrast, mice lacking Pyk2 [knockout (KO)] or treated with Pyk2 kinase inhibitor PF-431396 (PF) were protected. KO or PF-treated mice were also protected from GC-induced bone resorption, microarchitecture deterioration, and weakening of biomechanical properties. In KO and PF-treated mice, GC increased osteoclasts in bone and circulating tartrate-resistant acid phosphatase form 5b, an index of osteoclast number. However, bone surfaces covered by osteoclasts and circulating C-terminal telopeptides of type I collagen, an index of osteoclast function, were not increased. The mismatch between osteoclast number vs function induced by Pyk2 deficiency/inhibition was due to osteoclast detachment and anoikis. Further, GC prolongation of osteoclast lifespan was absent in KO and PF-treated osteoclasts, demonstrating Pyk2 as an intrinsic osteoclast-survival regulator. Circumventing Pyk2 activation preserves skeletal integrity by preventing GC effects on bone cell survival (proapoptotic for osteoblasts/osteocytes, antiapoptotic for osteoclasts) and GC-induced bone resorption. Thus, Pyk2/anoikis signaling as a therapeutic target for GC-induced osteoporosis.
Indexed as
Identifiers
What OpenQuestion holds
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.