Targeted Deletion of <i>Capn4</i> in Cells of the Chondrocyte Lineage Impairs Chondrocyte Proliferation and Differentiation

Kashiwagi, A; Schipani, Ernestina; Fein, Mikaela J.; Greer, Peter A.; Shimada, Masako

doi:10.1128/mcb.00157-10

Cited by 24 publications

(35 citation statements)

References 53 publications

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“…Therefore, the functional changes of chondrocytes play an important role by contributing to the degradation of the articular cartilage and thus to the pathogenesis of OA (15,16). Several studies have reported that there is a very low proliferative activity in osteoarthritic chondrocytes, which might be an efficient treatment to cure or even delay the progression of OA by promoting chondrocyte proliferation (17,18). Therefore, the present study has focused on chondrocyte proliferation and extends the clinical observations of the potential anti-cartilage degenerative effect of millimeter waves and establishes a scientific foundation for further research.…”

Section: Discussionmentioning

confidence: 99%

Millimeter wave treatment promotes chondrocyte proliferation via G1/S cell cycle transition

et al. 2012

Int J Mol Med

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Abstract. Millimeter waves, high-frequency electromagnetic waves, can effectively alleviate the clinical symptoms in osteoarthritis patients, as a non-pharmaceutical and non-invasive physical therapy regimen. However, the molecular mechanisms of the therapeutic effects of millimeter wave treatment are not well understood. In the present study, the effect of millimeter waves on the G 1 /S cell cycle progression in chondrocytes and the underlying mecha nism was investigated. Chondrocytes isolated from the knee of SD rats were cultured and identified using toluidine blue staining. The second generation chondrocytes were collected and stimulated with or without millimeter waves for 48 h. Chondrocyte viability was analyzed using the MTT assay. The cell cycle distribution of chondrocytes was analyzed by flow cytometry. mRNA and protein expression levels of cyclin D1, cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) and p21 were detected using real-time PCR and western blotting, respectively. Millimeter wave stimulation was found to significantly enhance chondrocyte viability. Moreover, the percentage of chondrocytes in the G 0 /G 1 phase was significantly decreased, whereas that in the S phase was significantly increased. In addition, following millimeter wave treatment, cyclin D1, CDK4 and CDK6 expression was significantly upregulated, whereas p21 expression was significantly downregulated. The results indicate that millimeter wave treatment promotes chondrocyte proliferation via cell cycle progression. IntroductionOsteoarthritis (OA), the most frequent arthropathy, is characterized by progressive degradation of hyaline articular cartilage and is associated with aging (1). A complex interplay of mechanical, and functional changes of chondrocytes could precipitate the imbalance between matrix anabolic and catabolic processes in articular cartilage and thus the pathogenesis of OA (2,3). Chondroctyes can rapidly respond to changes in the articular microenvironment and regulate the dynamic equilibrium between the anabolism and catabolism of the extracellular matrix (ECM), which plays a crucial role in the maintenance of the cartilage function (4). Therefore, enhancing chondrocyte function might be an efficient treatment to cure or even delay the progression of OA by promoting chondrocyte proliferation.The cell cycle plays an important role in the influence on chondrocyte function, which takes place in chondrocytes leading to its division and duplication. Cell cycle control is a highly regulated process that involves a complex cascade of events, in which regulation can be realized through a complicated network by cyclins, cyclin-dependent kinases (CDKs) and cyclin dependent kinase inhibitors (CDKI). G 1 /S transition, one of the two main checkpoints, is a rate-limiting step in the cell cycle and regulates cell proliferation (5,6). Cyclin D1 is a key cell cycle regulatory protein, which binds to CDK4 or CDK6 to control cell cycle progression from the G 1 to the S phase (7). Meanwhile, p21 competes with cyclin D1 for bindin...

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Section: Discussionmentioning

confidence: 99%

Millimeter wave treatment promotes chondrocyte proliferation via G1/S cell cycle transition

et al. 2012

Int J Mol Med

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“…We also observed reduced Akt phosphorylation and elevated PP2A levels in calpain 2-deficient AC2M2 cells, and this correlated with increased nuclear localization of FoxO3a and up-regulation of p27 Kip1 . Another recent study using conditional deletion of capns1 showed a role for calpain in embryonic chondrocyte proliferation (37). Disruption of calpain 1 and 2 in chondrocytes reduced cell cycle progression at G 1 /S transition, reduced cyclin D1 transcription, but enhanced the accumulation of cell cycle proteins cyclin D, cyclin E, and p27 Kip1 .…”

Section: Figure 6 Calpain 2 Regulates In Vivo P27mentioning

confidence: 97%

Calpain 2 Regulates Akt-FoxO-p27Kip1 Protein Signaling Pathway in Mammary Carcinoma

Pikor

Gao

et al. 2012

Journal of Biological Chemistry

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Background: Calpains are intracellular calcium-dependent proteases implicated in cancer. Results: Calpain 2 knockdown in breast cancer cells correlated with reduced in vitro proliferation, migration, and in vivo tumorigenicity as well as reduced Akt activation, increased nuclear FoxO localization, and increased p27 Kip1 expression. Conclusion: Calpain 2 promotes proliferation of cancer cells through Akt- Kip1 signaling. Significance: Calpain 2 represents a potential therapeutic target in breast cancer.

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“…Changes in chondrocyte function are critical for the degradation of articular cartilage and serve an important function in the pathogenesis of OA (4,5). Several studies have reported that there is reduced proliferative activity in osteoarthritic chondrocytes and thus promoting chondrocyte proliferation may be an efficient strategy to treat or delay the progression of OA (6,7).…”

Section: Introductionmentioning

confidence: 99%

Duhuo Jisheng Decoction-containing serum promotes proliferation of interleukin-1β-induced chondrocytes through the p16-cyclin D1/CDK4-Rb pathway

Fan

Huang

et al. 2014

Molecular Medicine Reports

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Duhuo Jisheng Decoction (DHJSD) is a traditional Chinese herbal medicine that has multiple uses, including as a treatment for osteoarthritis (OA). However, the molecular mechanisms underlying the therapeutic effects of DHJSD on OA remain unknown. In the present study, a serum pharmacological method was applied to investigate the effects of DHJSD on the proliferation of chondrocytes treated with interleukin‑1β (IL‑1β) in vitro. This is a cell model commonly used to reproduce the mechanisms involved in degenerative arthropathies, including OA. The most effective intervention conditions of DHJSD serum were examined by MTT assay. The degenerative chondrocyte model was established by IL‑1β‑culture for 24 h, and was verified by optical microscopy and immunohistochemical analyses. Following the successful establishment of the degenerative chondrocyte model, the chondrocytes were subsequently randomly divided into two groups: The blank serum group and the DHJSD treatment group. Subsequent to treatment with the corresponding serum, cell proliferation was detected by MTT assay and DNA staining followed by FACS analysis, and the mRNA and protein expression levels of cyclin D1, cyclin‑dependent kinase 4 (CDK4), retinoblastoma tumor suppressor protein (Rb) and p16 were measured by reverse transcription polymerase chain reaction and western blotting, respectively. The results indicated that the most effective condition for the promotion of chondrocyte proliferation was 10% concentration of DHJSD 2‑h serum, and the degenerative chondrocyte model was successfully reproduced by IL‑1β‑treatment for 24 h. The mRNA and protein expression levels of cyclin D1, CDK4 and Rb in the DHJSD serum‑treated cells were significantly increased compared with those in the blank serum group, whereas p16 expression was significantly downregulated. These results indicate that treatment of cells with DHJSD‑containing serum is able to promote IL‑1β‑induced chondrocyte proliferation by promoting G1/S phase transition via modulating the expressions of cyclin D1, CDK4, Rb and p16, which contribute to the clinical efficacy of DHJSD in OA.

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Targeted Deletion of Capn4 in Cells of the Chondrocyte Lineage Impairs Chondrocyte Proliferation and Differentiation

Cited by 24 publications

References 53 publications

Millimeter wave treatment promotes chondrocyte proliferation via G1/S cell cycle transition

Millimeter wave treatment promotes chondrocyte proliferation via G1/S cell cycle transition

Calpain 2 Regulates Akt-FoxO-p27Kip1 Protein Signaling Pathway in Mammary Carcinoma

Duhuo Jisheng Decoction-containing serum promotes proliferation of interleukin-1β-induced chondrocytes through the p16-cyclin D1/CDK4-Rb pathway

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