ArticleArthritis and rheumatism2008
Reduced limb length and worsened osteoarthritis in adult mice after genetic inhibition of p38 MAP kinase activity in cartilage.
Article in Arthritis and rheumatism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.Nature genetics · 2018Pooled it
- Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk.Cell genomics · 2025Article
- Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk.bioRxiv : the preprint server for biology · 2024Article
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- FoxO1 is a crucial mediator of TGF-β/TAK1 signaling and protects against osteoarthritis by maintaining articular cartilage homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Big data boost for osteoarthritis genetics.Nature reviews. Rheumatology · 2018Article
- TGFβ signaling in cartilage development and maintenance.Birth defects research. Part C, Embryo today : reviews · 2014Review
- Extracellular and intracellular mechanisms of mechanotransduction in three-dimensionally embedded rat chondrocytes.PloS one · 2014Article
- TAK1 regulates SOX9 expression in chondrocytes and is essential for postnatal development of the growth plate and articular cartilages.Journal of cell science · 2013Article
- Cyclic compression-induced p38 activation and subsequent MMP13 expression requires Rho/ROCK activity in bovine cartilage explants.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2012Article
- Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathway.Arthritis research & therapy · 2012Article
- Subcellular relocation of histone deacetylase 4 regulates growth plate chondrocyte differentiation through Ca2+/calmodulin-dependent kinase IV.American journal of physiology. Cell physiology · 2012Article
- Vinculin functions as regulator of chondrogenesis.The Journal of biological chemistry · 2012Article
- Intracellular modulation of signaling pathways by annexin A6 regulates terminal differentiation of chondrocytes.The Journal of biological chemistry · 2012Article
- p38gamma mitogen-activated protein kinase suppresses chondrocyte production of MMP-13 in response to catabolic stimulation.Osteoarthritis and cartilage · 2010Article
- TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2010Article
- Aberrant hypertrophy in Smad3-deficient murine chondrocytes is rescued by restoring transforming growth factor beta-activated kinase 1/activating transcription factor 2 signaling: a potential clinical implication for osteoarthritis.Arthritis and rheumatism · 2010Article
- Biology and pathology of Rho GTPase, PI-3 kinase-Akt, and MAP kinase signaling pathways in chondrocytes.Journal of cellular biochemistry · 2010Review
- Are endogenous BMPs necessary for bone healing during distraction osteogenesis?Clinical orthopaedics and related research · 2009Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveMAP kinase p38 is part of an intracellular signaling pathway activated by environmental stress and inflammatory factors. Since in vitro studies show that inhibiting p38 activity leads to a reduction in the release of degenerative metalloproteinase from chondrocytes, we speculated that inactivation of p38 in vivo may be chondroprotective. To test this hypothesis, we examined the morphology of adult mice that express a dominant-negative (DN) p38 MAPK transgene in a cartilage-specific manner.
methodsThe in vivo effects of the genetic inhibition of p38 MAPK activity in cartilage were investigated in 1-year-old heterozygous DN p38-transgenic mice (n = 10) using morphologic measurements, microfocal computed tomography scanning, biomechanical testing, and histologic analysis. Results were compared with those in wild-type (WT) littermates (n = 9).
resultsAdult DN p38 MAPK+/- -transgenic mice exhibited 50% p38 MAPK activity in articular chondrocytes as compared with WT mice. They were significantly shorter in overall body length as well as in the femur and tibia lengths. There were no differences in bone material or mechanical properties between the transgenic and WT mice. Surprisingly, the transgenic mice had higher grades of osteoarthritis of the knee joint.
conclusionGenetic inhibition of p38 MAPK activity in cartilage results in shortened limb length and defects in the articular cartilage of the knee joints of adult mice. Our findings demonstrate that chronic life-long reduction of p38 MAPK activity may be harmful to joint health and suggest that the timing of p38 inhibition for chondroprotection in vivo is an important variable that warrants further investigation.
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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.