ArticleArthritis and rheumatism2009
Increased expression of the Akt/PKB inhibitor TRB3 in osteoarthritic chondrocytes inhibits insulin-like growth factor 1-mediated cell survival and proteoglycan synthesis.
Article in Arthritis and rheumatism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 95 citations in OpenAlex.
- Cartilage degeneration is associated with activation of the PI3K/AKT signaling pathway in a growing rat experimental model of developmental trochlear dysplasia.Journal of advanced research · 2022Trial
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- Platelet-rich plasma in cartilage repair: biological mechanisms and clinical perspectives.Frontiers in sports and active living · 2026Review
- High-intensity running exercise promotes knee meniscal damage via the PI3K/AKT/mTOR axis.Bone & joint research · 2025Article
- Mechanism of action and new developments in the study of curcumin in the treatment of osteoarthritis: a narrative review.Inflammopharmacology · 2025Review
- Platelet-rich plasma combined with isometric quadriceps contraction regulates autophagy in chondrocytes via the PI3K/AKT/mTOR pathway to promote cartilage repair in knee osteoarthritis.Regenerative therapy · 2025Article
- Exosomes in cartilage microenvironment regulation and cartilage repair.Frontiers in cell and developmental biology · 2025Review
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- Endoplasmic reticulum stress-mediated apoptosis and autophagy in osteoarthritis: From molecular mechanisms to therapeutic applications.Cell stress & chaperones · 2024Review
- Targeting PI3K/Akt in Cerebral Ischemia Reperfusion Injury Alleviation: From Signaling Networks to Targeted Therapy.Molecular neurobiology · 2024Review
- 2D MXene Nanosheets with ROS Scavenging Ability Effectively Delay Osteoarthritis Progression.Nanomaterials (Basel, Switzerland) · 2024Article
- Effect of umbilical cord blood-mononuclear cells on knee osteoarthritis in rabbits.Journal of orthopaedic surgery and research · 2024Article
- Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases.Military Medical Research · 2023Review
- Low back pain and osteoarthritis pain: a perspective of estrogen.Bone research · 2023Review
- Glycolysis: an emerging regulator of osteoarthritis.Frontiers in immunology · 2023Review
- High TRB3 expression induces chondrocyte autophagy and senescence in osteoarthritis cartilage.Aging · 2022Article
- Kindlin-2 Promotes Chondrogenesis and Ameliorates IL-1beta-Induced Inflammation in Chondrocytes Cocultured with BMSCs in the Direct Contact Coculture System.Oxidative medicine and cellular longevity · 2022Article
- A bibliometrics analysis and visualization of osteoimmunology on osteoarthritis studies.American journal of translational research · 2022Article
- The Recovery of Cognitive and Affective Deficiencies Linked with Chronic Osteoarthritis Pain and Implicated Pathways by Slow-Releasing Hydrogen Sulfide Treatment.Antioxidants (Basel, Switzerland) · 2021Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveThe chondrocyte response to insulin-like growth factor 1 (IGF-1) is reduced with aging and in osteoarthritis (OA). IGF-1 signals through the phosphatidylinositol 3-kinase/Akt pathway. TRB3, a tribbles homolog, has been shown to inhibit IGF-1-mediated activation of Akt in HEK 293 cells. This study was undertaken to determine if TRB3 is expressed in chondrocytes, and whether the chondrocyte response to IGF-1 is reduced by TRB3.
methodsHuman articular cartilage was obtained from normal tissue donors and from patients with OA at the time of knee replacement surgery. TRB3 was assessed in the tissue samples by reverse transcription-polymerase chain reaction, immunoblotting, and immunohistochemistry. Overexpression of TRB3 was induced by transient transfection to determine the effects of TRB3 on cell survival and proteoglycan synthesis.
resultsTRB3 messenger RNA was detected in normal human chondrocytes. TRB3 protein levels were low in cells from normal cartilage but significantly increased in cells from OA cartilage. Incubation with 2 agents that induce endoplasmic reticulum stress, tunicamycin and thapsigargin, increased TRB3 levels in normal cells. Overexpression of TRB3 inhibited Akt phosphorylation and reduced chondrocyte survival and proteoglycan synthesis.
conclusionThese results are the first to demonstrate that TRB3 is present in human chondrocytes, and that the level of TRB3 is increased in OA cartilage and in isolated OA chondrocytes. Because it is an inhibitor of Akt activation, elevated TRB3 production could play a role in the increased cell death and reduced response to IGF-1 observed in OA cartilage.
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