ArticlePloS one2014
Differential roles of MAPK kinases MKK3 and MKK6 in osteoclastogenesis and bone loss.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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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
22 citing papers in PubMed, 32 citations in OpenAlex.
- Clustered peptide regulating the multivalent interaction between RANK and TRAF6 inhibits osteoclastogenesis by fine-tuning signals.Communications biology · 2025Article
- Phospholipase C β4 promotes RANKL-dependent osteoclastogenesis by interacting with MKK3 and p38 MAPK.Experimental & molecular medicine · 2025Article
- Oxyresveratrol attenuates bone resorption by inhibiting the mitogen-activated protein kinase pathway in ovariectomized rats.Nutrition & metabolism · 2024Article
- Suppression of CGRP and TRPV1 Expression in Dorsal Root Ganglia of Knee Osteoarthritis Rats by Huojing Decoction via TrkA/MKK3/6/p38 Pathway.Journal of inflammation research · 2024Article
- Loureirin B downregulates osteoclast differentiation of bone marrow macrophages by targeting the MAPK signaling pathway.Scientific reports · 2022Article
- Isoliensinine Suppresses Osteoclast Formation Through NF-κB Signaling Pathways and Relieves Ovariectomy-Induced Bone Loss.Frontiers in pharmacology · 2022Article
- [Zoledronate regulates osteoclast differentiation and bone resorption in high glucose through p38 MAPK pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- High expression of MKK3 is associated with worse clinical outcomes in African American breast cancer patients.Journal of translational medicine · 2020Article
- MKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer.Cell death & disease · 2019Article
- Inhibition of Osteoclastogenesis by Thioredoxin-Interacting Protein-Derived Peptide (TN13).Journal of clinical medicine · 2019Article
- Cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesis.Lupus science & medicine · 2019Article
- Roles of Mitogen-Activated Protein Kinases in Osteoclast Biology.International journal of molecular sciences · 2018Review
- Identification of miR-708-5p in peripheral blood monocytes: Potential marker for postmenopausal osteoporosis in Mexican-Mestizo population.Experimental biology and medicine (Maywood, N.J.) · 2018Article
- Insights of Crosstalk between p53 Protein and the MKK3/MKK6/p38 MAPK Signaling Pathway in Cancer.Cancers · 2018Review
- Recent advances in osteoclast biology.Histochemistry and cell biology · 2018Review
- Roles of Wnt3a and Dkk1 in experimental periodontitis.Journal of dental sciences · 2017Article
- p38α MAPK regulates proliferation and differentiation of osteoclast progenitors and bone remodeling in an aging-dependent manner.Scientific reports · 2017Article
- Relationship between osteogenesis and angiogenesis in ovariectomized osteoporotic rats after exercise training.International journal of clinical and experimental pathology · 2017Article
- miR-434-3p and DNA hypomethylation co-regulate eIF5A1 to increase AChRs and to improve plasticity in SCT rat skeletal muscle.Scientific reports · 2016Article
- Focus on the p38 MAPK signaling pathway in bone development and maintenance.BoneKEy reports · 2015Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
Bone mass is maintained by osteoclasts that resorb bone and osteoblasts that promote matrix deposition and mineralization. Bone homeostasis is altered in chronic inflammation as well as in post-menopausal loss of estrogen, which favors osteoclast activity that leads to osteoporosis. The MAPK p38α is a key regulator of bone loss and p38 inhibitors preserve bone mass by inhibiting osteoclastogenesis. p38 function is regulated by two upstream MAPK kinases, namely MKK3 and MKK6. The goal of this study was to assess the effect of MKK3- or MKK6-deficiency on osteoclastogenesis in vitro and on bone loss in ovariectomy-induced osteoporosis in mice. We demonstrated that MKK3 but not MKK6, regulates osteoclast differentiation from bone marrow cells in vitro. Expression of NFATc1, a master transcription factor in osteoclastogenesis, is decreased in cells lacking MKK3 but not MKK6. Expression of osteoclast-specific genes Cathepsin K, osteoclast-associated receptor and MMP9, was inhibited in MKK3-/- cells. The effect of MKK-deficiency on ovariectomy-induced bone loss was then evaluated in female WT, MKK3-/- and MKK6-/- mice by micro-CT analysis. Bone loss was partially inhibited in MKK3-/- as well as MKK6-/- mice, despite normal osteoclastogenesis in MKK6-/- cells. This correlated with the lower osteoclast numbers in the MKK-deficient ovariectomized mice. These studies suggest that MKK3 and MKK6 differentially regulate bone loss due to estrogen withdrawal. MKK3 directly mediates osteoclastogenesis while MKK6 likely contributes to pro-inflammatory cytokine production that promotes osteoclast formation.
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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.