Increased apoptosis in human knee osteoarthritis cartilage related to the expression of protein kinase B and protein kinase Cα in chondrocytes

Chen, Qingzhi; Zhang, Bing; Yi, Tingting; Xia, Chun

doi:10.5603/fhc.2012.0020

Cited by 21 publications

(16 citation statements)

References 25 publications

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“…Finally, dark brown cells were considered to be positive, and were counted throughout microscopically magnified fields (×400) of each articular cartilage section. The percentage of positive cells was analyzed by SPSS v.15.0 for Windows [25]. …”

Section: Methodsmentioning

confidence: 99%

Disruption of Phosphoinositide-Specific Phospholipases Cγ1 Contributes to Extracellular Matrix Synthesis of Human Osteoarthritis Chondrocytes

Zeng

Cui

Liu

et al. 2014

IJMS

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Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation including extracellular matrix (ECM) degradation and cell loss. It is known that phosphoinositide-specific phospholipase γ1 (PLCγ1) can trigger several signaling pathways to regulate cell metabolism. However, whether this kinase is expressive and active in human OA chondrocytes and its role in the pathological progression of OA have not been investigated. The current study was designed to investigate the PLCγ1 expression in human OA cartilage, and whether PLCγ1 was involved in the ECM synthesis had been further explored using cultured human OA chondrocytes. Our results indicated that PLCγ1 was highly expressed in human OA chondrocytes. In our further study using the cultured human OA chondrocytes, the results demonstrated that the disruption of PLCγ1 by its inhibitor, U73122, and siRNA contributed to the ECM synthesis of human OA chondrocytes through regulating the expression of ECM-related signaling molecules, including MMP-13, Col II, TIMP1, Sox-9, and AGG. Furthermore, PLCγ1/IP3/Ca(2+)/CaMK II signaling axis regulated the ECM synthesis of human chondrocytes through triggering mTOR/P70S6K/S6 pathway. In summary, our results suggested that PLC-γ1 activities played an important role in the ECM synthesis of human OA chondrocytes, and may serve as a therapeutic target for treating OA.

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Section: Methodsmentioning

confidence: 99%

Disruption of Phosphoinositide-Specific Phospholipases Cγ1 Contributes to Extracellular Matrix Synthesis of Human Osteoarthritis Chondrocytes

Zeng

Cui

Liu

et al. 2014

IJMS

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“…It is possible that STAT3-independent, JAK2-dependent mechanisms also contribute to the antiapoptotic effect of PRL. Activation of JAK2 by PRL stimulates PI3K/Akt to promote the survival of various cells (39)(40)(41)(42), and activation of Akt inhibits the apoptosis of chondrocytes induced by endoplasmic reticulum stress or the osteoarthritic condition (43,44).…”

Section: Discussionmentioning

confidence: 99%

Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

et al. 2013

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Chondrocytes are the only cells in cartilage, and their death by apoptosis contributes to cartilage loss in inflammatory joint diseases, such as rheumatoid arthritis (RA). A putative therapeutic intervention for RA is the inhibition of apoptosis-mediated cartilage degradation. The hormone prolactin (PRL) frequently increases in the circulation of patients with RA, but the role of hyperprolactinemia in disease activity is unclear. Here, we demonstrate that PRL inhibits the apoptosis of cultured chondrocytes in response to a mixture of proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) by preventing the induction of p53 and decreasing the BAX/BCL-2 ratio through a NO-independent, JAK2/STAT3-dependent pathway. Local treatment with PRL or increasing PRL circulating levels also prevented chondrocyte apoptosis evoked by injecting cytokines into the knee joints of rats, whereas the proapoptotic effect of cytokines was enhanced in PRL receptor-null (Prlr -/-) mice. Moreover, eliciting hyperprolactinemia in rats before or after inducing the adjuvant model of inflammatory arthritis reduced chondrocyte apoptosis, proinflammatory cytokine expression, pannus formation, bone erosion, joint swelling, and pain. These results reveal the protective effect of PRL against inflammation-induced chondrocyte apoptosis and the therapeutic potential of hyperprolactinemia to reduce permanent joint damage and inflammation in RA.

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“…The immunohistochemistry was performed as described previously [17,18]. The tissue microarray was deparaffinised in xylene and rehydrated in graded alcohols and distilled water.…”

mentioning

confidence: 99%

Metastasis of human gastric adenocarcinoma partly depends on phosphoinositide-specific phospholipase γ1 expression

Zhuang

Zhang²,

Zeng³

et al. 2014

Folia Histochem Cytobiol.

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Abstract:It is known that phosphoinositide-specific phospholipases g1 (PLCg1) can trigger several signalling pathways to regulate cell proliferation, differentiation, and metastasis. However, whether this kinase is highly expressive and active in human gastric adenocarcinomas, and whether it can play an important role in the development of the cancer, have not yet been investigated. The aim of the study was to investigate the expression of PLCg1 in human gastric adenocarcinoma, while the question of whether PLCg1 can be activated through protein kinase B (Akt) signalling pathways to regulate cell migration was further explored using human gastric adenocarcinoma BGC-823 cell line. The expression of PLCg1 in human adenocarcinoma was detected using immunohistochemical staining. The BGC-823 cells were cultured and treated with inhibitors or transfected with plasmid construction. The cell migration of BGC-823 cells was measured with wound healing assay, cell migration assay, and the ruffling assay. The expression levels of PLCg1 and its related signal molecules in BGC-823 cells were assessed using Western blot analysis or gelatine zymography assay. PLCg1 was highly expressed in human gastric adenocarcinomas, especially in the region with lymph node metastasis. It was shown that migration of BGC-823 cells in vitro depends on PLCg1 activation. This activation is mediated through Akt, an upstream of PLCg1 that triggers the PLCg1/extracellular signal-regulated kinase (ERK)/matrix metalloproteinase (MMP) pathway in BGC-823 cells. PLCg1 activities play an important role in the metastasis of gastric adenocarcinoma, and may serve as a potential therapeutic target in this type of cancer.

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Increased apoptosis in human knee osteoarthritis cartilage related to the expression of protein kinase B and protein kinase Cα in chondrocytes

Cited by 21 publications

References 25 publications

Disruption of Phosphoinositide-Specific Phospholipases Cγ1 Contributes to Extracellular Matrix Synthesis of Human Osteoarthritis Chondrocytes

Disruption of Phosphoinositide-Specific Phospholipases Cγ1 Contributes to Extracellular Matrix Synthesis of Human Osteoarthritis Chondrocytes

Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

Metastasis of human gastric adenocarcinoma partly depends on phosphoinositide-specific phospholipase γ1 expression

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