ArticleOsteoarthritis and cartilage2019
CaMKII inhibition in human primary and pluripotent stem cell-derived chondrocytes modulates effects of TGFβ and BMP through SMAD signaling.
Article in Osteoarthritis and cartilage, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Obesity-induced oleic acid metabolic dysregulation may exacerbate osteoarthritis through the degradation of SOX9.Cellular and molecular life sciences : CMLS · 2026Article
- CaMKII phosphorylation promotes renal fibrosis in cisplatin induced chronic kidney disease via Smad 2/3 activation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Spatiotemporal Regulation and Lineage Specification in Embryonic Endochondral Ossification.International journal of molecular sciences · 2026Review
- Piezo1 selectively enhances TGF-β1-induced IgA class switching by B cells.Cellular and molecular life sciences : CMLS · 2025Article
- Insights into the bone morphogenetic protein signaling in musculoskeletal disorders: Mechanisms and crosstalk.Journal of orthopaedic translation · 2025Review
- Article
- Cinnamaldehyde Alleviates Alveolar Epithelial Cell Injury in ALI by Inhibiting the CaMKII Pathway.Cell biochemistry and biophysics · 2025Article
- TMF suppresses chondrocyte hypertrophy in osteoarthritic cartilage by mediating the FOXO3a/BMPER pathway.Experimental and therapeutic medicine · 2024Article
- Proteoglycan inhibition of canonical BMP-dependent cartilage maturation delays endochondral ossification.Development (Cambridge, England) · 2024Article
- CaMKII inhibition due to TRIC-B loss-of-function dysregulates SMAD signaling in osteogenesis imperfecta.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Wnt signalling in the articular cartilage: A matter of balance.International journal of experimental pathology · 2023Review
- Adipokine Signaling Pathways in Osteoarthritis.Frontiers in bioengineering and biotechnology · 2022Review
- Lack of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Disturbs Callus Formation.Journal of molecular neuroscience : MN · 2021Article
- Article
- Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis.Scientific reports · 2021Article
- Targeting miR-18a sensitizes chondrocytes to anticytokine therapy to prevent osteoarthritis progression.Cell death & disease · 2020Article
- Melatonin modulates proliferation of pancreatic stellate cells through caspase-3 activation and changes in cyclin A and D expression.Journal of physiology and biochemistry · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveUpregulation of calcium/calmodulin-dependent kinase II (CaMKII) is implicated in the pathogenesis of osteoarthritis (OA) and reactivation of articular cartilage hypertrophy. However, direct inhibition of CaMKII unexpectedly augmented symptoms of OA in animal models. The role of CaMKII in OA remains unclear and requires further investigation.
methodsAnalysis of CaMKII expression was performed in normal human and OA articular chondrocytes, and signaling mechanisms were assessed in articular, fetal and Pluripotent Stem Cell (PSC)-derived human chondrocytes using pharmacological (KN93), peptide (AC3-I) and small interfering RNA (siRNA) inhibitors of CaMKII.
resultsExpression levels of phospho-CaMKII (pCaMKII) were significantly and consistently increased in human OA specimens. BMP2/4 activated expression of pCaMKII as well as COLII and COLX in human adult articular chondrocytes, and also increased the levels and nuclear localization of SMADs1/5/8, while TGFβ1 showed minimal or no activation of the chondrogenic program in adult chondrocytes. Targeted blockade of CaMKII with specific siRNAs decreased levels of pSMADs, COLII, COLX and proteoglycans in normal and OA adult articular chondrocytes in the presence of both BMP4 and TGFβ1. Both human fetal and PSC-derived chondrocytes also demonstrated a decrease of chondrogenic differentiation in the presence of small molecule and peptide inhibitors of CaMKII. Furthermore, immunoprecipitation for SMADs1/5/8 or 2/3 followed by western blotting for pCaMKII showed direct interaction between SMADs and pCaMKII in primary chondrocytes.
conclusionCurrent study demonstrates a direct role for CaMKII in TGF-β and BMP-mediated responses in primary and PSC-derived chondrocytes. These findings have direct implications for tissue engineering of cartilage tissue from stem cells and therapeutic management of OA.
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