The role of the PKCζ/JNK signaling pathway in regulating the development of femoral head necrosis
Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by the death of bone cells in the hip joint, resulting in profound disability. This condition has a significant global prevalence. Glucocorticoid (GC)-induced apoptosis of bone cells serves as a crucial cellular mecha...
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Associação Brasileira de Divulgação Científica
2025-03-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100622&lng=en&tlng=en |
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| author | Miaofeng Hu Cheng Li Qi Sun Baisong Hu Jiong Yang Xiufeng Wang Jinshan Huang Di Shen |
| author_facet | Miaofeng Hu Cheng Li Qi Sun Baisong Hu Jiong Yang Xiufeng Wang Jinshan Huang Di Shen |
| author_sort | Miaofeng Hu |
| collection | DOAJ |
| description | Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by the death of bone cells in the hip joint, resulting in profound disability. This condition has a significant global prevalence. Glucocorticoid (GC)-induced apoptosis of bone cells serves as a crucial cellular mechanism underlying ONFH. The protein kinase C zeta (PKCζ) and c-Jun N-terminal kinase (JNK)/c-Jun cascades have been implicated in the progression of ONFH, yet their interrelationship and contributions to disease development remain unclear. The objective of this study was to investigate the combined impact of PKCζ and JNK/c-Jun signaling on dexamethasone (Dex)-induced apoptosis in osteoblasts in vitro and in GC-induced ONFH rat models in vivo. In vitro experiments were conducted using hFOB1.19 osteoblastic cells to scrutinize the effects of Dex-induced apoptosis. The role of the PKCζ/JNK/c-Jun signaling pathway in this process was examined using naringenin-7-O-β-D-Glucuronide (N7G), a PKC inhibitor, and anisomycin, a JNK activator. The findings were further validated using a rat model of ONFH in vivo. Our results revealed that PKCζ activation augmented JNK/c-Jun signaling and facilitated Dex-induced osteoblast apoptosis. Inhibition of PKCζ with N7G mitigated these effects, while JNK activation with anisomycin intensified them. Similar regulatory effects on osteoblast apoptosis and ONFH progression were observed in the in vivo rat models. Glucocorticoids can induce osteoblast apoptosis and contribute to the development of ONFH by activating the PKCζ/JNK/c-Jun signaling pathway. This study provides compelling evidence supporting the potential therapeutic value of comprehending the pathogenesis of ONFH and developing targeted treatments for this debilitating condition. |
| format | Article |
| id | doaj-art-44b5d4591c1e4b00a7ac0ee93c3b19a9 |
| institution | DOAJ |
| issn | 1414-431X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj-art-44b5d4591c1e4b00a7ac0ee93c3b19a92025-08-20T03:15:47ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2025-03-015810.1590/1414-431x2025e13771The role of the PKCζ/JNK signaling pathway in regulating the development of femoral head necrosisMiaofeng Huhttps://orcid.org/0009-0005-0064-2219Cheng Lihttps://orcid.org/0009-0000-4872-2131Qi Sunhttps://orcid.org/0009-0007-3914-9047Baisong Huhttps://orcid.org/0009-0007-0350-6639Jiong Yanghttps://orcid.org/0009-0002-5397-1364Xiufeng Wanghttps://orcid.org/0009-0004-6435-1309Jinshan Huanghttps://orcid.org/0009-0003-1748-7740Di Shenhttps://orcid.org/0009-0007-7359-7441Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by the death of bone cells in the hip joint, resulting in profound disability. This condition has a significant global prevalence. Glucocorticoid (GC)-induced apoptosis of bone cells serves as a crucial cellular mechanism underlying ONFH. The protein kinase C zeta (PKCζ) and c-Jun N-terminal kinase (JNK)/c-Jun cascades have been implicated in the progression of ONFH, yet their interrelationship and contributions to disease development remain unclear. The objective of this study was to investigate the combined impact of PKCζ and JNK/c-Jun signaling on dexamethasone (Dex)-induced apoptosis in osteoblasts in vitro and in GC-induced ONFH rat models in vivo. In vitro experiments were conducted using hFOB1.19 osteoblastic cells to scrutinize the effects of Dex-induced apoptosis. The role of the PKCζ/JNK/c-Jun signaling pathway in this process was examined using naringenin-7-O-β-D-Glucuronide (N7G), a PKC inhibitor, and anisomycin, a JNK activator. The findings were further validated using a rat model of ONFH in vivo. Our results revealed that PKCζ activation augmented JNK/c-Jun signaling and facilitated Dex-induced osteoblast apoptosis. Inhibition of PKCζ with N7G mitigated these effects, while JNK activation with anisomycin intensified them. Similar regulatory effects on osteoblast apoptosis and ONFH progression were observed in the in vivo rat models. Glucocorticoids can induce osteoblast apoptosis and contribute to the development of ONFH by activating the PKCζ/JNK/c-Jun signaling pathway. This study provides compelling evidence supporting the potential therapeutic value of comprehending the pathogenesis of ONFH and developing targeted treatments for this debilitating condition.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100622&lng=en&tlng=enOsteonecrosis of the femoral headGlucocorticoidOsteoblast apoptosisPKCζJNK |
| spellingShingle | Miaofeng Hu Cheng Li Qi Sun Baisong Hu Jiong Yang Xiufeng Wang Jinshan Huang Di Shen The role of the PKCζ/JNK signaling pathway in regulating the development of femoral head necrosis Brazilian Journal of Medical and Biological Research Osteonecrosis of the femoral head Glucocorticoid Osteoblast apoptosis PKCζ JNK |
| title | The role of the PKCζ/JNK signaling pathway in regulating the development of femoral head necrosis |
| title_full | The role of the PKCζ/JNK signaling pathway in regulating the development of femoral head necrosis |
| title_fullStr | The role of the PKCζ/JNK signaling pathway in regulating the development of femoral head necrosis |
| title_full_unstemmed | The role of the PKCζ/JNK signaling pathway in regulating the development of femoral head necrosis |
| title_short | The role of the PKCζ/JNK signaling pathway in regulating the development of femoral head necrosis |
| title_sort | role of the pkcζ jnk signaling pathway in regulating the development of femoral head necrosis |
| topic | Osteonecrosis of the femoral head Glucocorticoid Osteoblast apoptosis PKCζ JNK |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100622&lng=en&tlng=en |
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