PI3K/AKT信号通路调控DDH脱位后软骨细胞自噬的相关研究
Research on the Regulation of Chondrocyte Autophagy after DDH Dislocation by the PI3K/AKT Signaling Pathway
DOI: 10.12677/acm.2024.1441305, PDF,   
作者: 郭 宇, 祁 凯, 陈云鹏, 黄志明, 王伟豪, 韦宜山*:内蒙古医科大学第二附属医院,内蒙古 呼和浩特
关键词: PI3K/AKT发育性髋关节脱位自噬软骨细胞PI3K/AKT Developmental Hip Dislocation Autophagy Chondrocytes
摘要: 发育性髋关节脱位(development dislocation of the hip, DDH),是在髋关节发育不良的基础上,伴有或不伴有股骨头脱位或半脱位于髋臼之外的下肢畸形。其病理改变不同可能会导致严重程度不一的早期骨关节炎(osteoarthritis, OA)。DDH的一个重要病理变化是关节软骨的退化及退变,但目前关于DDH软骨退变的机制尚未明确。一些研究发现软骨细胞的自噬与骨关节炎密切相关,其中PI3K/AKT信号通路可以促进软骨细胞增殖,并且抑制软骨细胞自噬。本文旨在探讨PI3K/AKT信号通路对软骨细胞自噬的调控作用,为DDH后期的诊疗提供新的思路。
Abstract: Developmental dislocation of the hip (DDH) is a lower limb deformity located outside the acetabulum, with or without dislocation or subluxation of the femoral head, on the basis of hip dysplasia. Different pathological changes may lead to early osteoarthritis (OA) with varying degrees of severity. One important pathological change of DDH is the degradation and degeneration of articular cartilage, but the mechanism of DDH cartilage degeneration is currently unclear. Some studies have found that autophagy of chondrocytes is closely related to osteoarthritis, among which the PI3K/AKT signaling pathway can promote chondrocyte proliferation and inhibit chondrocyte autophagy. This article aims to explore the regulatory role of the PI3K/AKT signaling pathway on chondrocyte autophagy, providing new ideas for the diagnosis and treatment of DDH in the later stage.
文章引用:郭宇, 祁凯, 陈云鹏, 黄志明, 王伟豪, 韦宜山. PI3K/AKT信号通路调控DDH脱位后软骨细胞自噬的相关研究[J]. 临床医学进展, 2024, 14(4): 2385-2389. https://doi.org/10.12677/acm.2024.1441305

参考文献

[1] Wei, Y.S., Li, D.H., Liu, W.L. and Jiang, D.M. (2016) Altered Chondrocyte Apoptosis Status in Developmental Hip Dysplasia in Rabbits. Balkan Medical Journal, 33, 639-644. [Google Scholar] [CrossRef] [PubMed]
[2] Vaquero-Picado, A., González-Morán, G., Garay, E.G. and Moraleda, L. (2019) Developmental Dysplasia of the Hip: Update of Management. EFORT Open Reviews, 4, 548-556. [Google Scholar] [CrossRef] [PubMed]
[3] Hawker, G.A. (2019) Osteoarthritis Is a Serious Disease. Clinical and Experimental Rheumatology, 37, 3-6.
[4] Lorenz, H. and Richter, W. (2006) Osteoarthritis: Cellular and Molecular Changes in Degenerating Cartilage. Progress in Histochemistry and Cytochemistry, 40, 135-163. [Google Scholar] [CrossRef] [PubMed]
[5] 宁波. β-catenin在发育性髋关节脱位动物模型早期软骨退行性变中机制的实验研究[D]: [博士学位论文]. 上海: 复旦大学, 2013.
[6] Zhang, Q., Lai, S., Hou, X., Cao, W., Zhang, Y. and Zhang, Z. (2018) Protective Effects of PI3K/Akt Signal Pathway Induced Cell Autophagy in Rat Knee Joint Cartilage Injury. American Journal of Translational Research, 10, 762-770.
[7] Carney, B.T. (2005) Acetabular Dysplasia Following Closed Reduction of Developmental Dislocation of the Hip. Journal of Surgical Orthopaedic Advances, 14, 122-124.
[8] Thomas, S.R., Wedge, J.H. and Salter, R.B. (2007) Outcome at Forty-Five Years after Open Reduction and Innominate Osteotomy for Late-Presenting Developmental Dislocation of the Hip. The Journal of Bone and Joint Surgery, 89, 2341-2350. [Google Scholar] [CrossRef
[9] Martel-Pelletier, J., Boileau, C., Pelletier, J.P. and Roughley, P.J. (2008) Cartilage in Normal and Osteoarthritis Conditions. Best Practice & Research Clinical Rheumatology, 22, 351-384. [Google Scholar] [CrossRef] [PubMed]
[10] Huang, J.G., Xia, C., Zheng, X.P., Yi, T.T., Wang, X.Y., Song, G. and Zhang, B. (2011) 17β-Estradiol Promotes Cell Proliferation in Rat Osteoarthritis Model Chondrocytes via PI3K/Akt Pathway. Cellular & Molecular Biology Letters, 16, 564-575. [Google Scholar] [CrossRef] [PubMed]
[11] Ozgur, A.F., Aksoy, M.C., Kandemir, U., Karcaaltncaba, M., Aydingoz, U., Yazici, M. and Surat, A. (2006) Does Dega Osteotomy Increase Acetabular Volume in Developmental Dysplasia of the Hip? Journal of Pediatric Orthopaedics B, 15, 83-86. [Google Scholar] [CrossRef] [PubMed]
[12] Yan, W., Zheng, L., Xu, X., et al. (2022) Heterozygous LRP1 Deficiency Causes Developmental Dysplasia of the Hip by Impairing Triradiate Chondrocytes Differentiation Due to Inhibition of Autophagy. Proceedings of the National Academy of Sciences of the United States of America, 119, e2203557119. [Google Scholar] [CrossRef] [PubMed]
[13] Hwang, H.S. and Kim, H.A. (2015) Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis. International Journal of Molecular Sciences, 16, 26035-26054. [Google Scholar] [CrossRef] [PubMed]
[14] Garvican, E.R., Vaughan-Thomas, A., Innes, J.F. and Clegg, P.D. (2010) Biomarkers of Cartilage Turnover. Part 1: Markers of Collagen Degradation and Synthesis. The Veterinary Journal, 185, 36-42. [Google Scholar] [CrossRef] [PubMed]
[15] Garvican, E.R., Vaughan-Thomas, A., Clegg, P.D. and Innes, J.F. (2010) Biomarkers of Cartilage Turnover. Part 2: Non-Collagenous Markers. The Veterinary Journal, 185, 43-49. [Google Scholar] [CrossRef] [PubMed]
[16] Brandt, K.D., Dieppe, P. and Radin, E.L. (2008) Etiopathogenesis of Osteoarthritis. Rheumatic Disease Clinics of North America, 34, 531-559. [Google Scholar] [CrossRef] [PubMed]
[17] Guilak, F., Nims, R.J., Dicks, A., Wu, C.L. and Meulenbelt, I. (2018) Osteoarthritis as a Disease of the Cartilage Pericellular Matrix. Matrix Biology, 71-72, 40-50. [Google Scholar] [CrossRef] [PubMed]
[18] Rim, Y.A. and Ju, J.H. (2020) The Role of Fibrosis in Osteoarthritis Progression. Life, 11, Article 3. [Google Scholar] [CrossRef] [PubMed]
[19] Withrow, J., Murphy, C., Liu, Y., Hunter, M., Fulzele, S. and Hamrick, M.W. (2016) Extracellular Vesicles in the Pathogenesis of Rheumatoid Arthritis and Osteoarthritis. Arthritis Research & Therapy, 18, Article No. 286. [Google Scholar] [CrossRef] [PubMed]
[20] Zhao, P., Dou, Y., Chen, L., Li, L., Wei, Z., Yu, J., Wu, X., Dai, Y. and Xia, Y. (2015) SC-III3, a Novel Scopoletin Derivative, Induces Autophagy of Human Hepatoma HepG2 Cells through AMPK/mTOR Signaling Pathway by Acting on Mitochondria. Fitoterapia, 104, 31-40. [Google Scholar] [CrossRef] [PubMed]
[21] Rubinsztein, D.C., Mariño, G. and Kroemer, G. (2011) Autophagy and Aging. Cell, 146, 682-695. [Google Scholar] [CrossRef] [PubMed]
[22] Degenhardt, K., Mathew, R., Beaudoin, B., et al. (2006) Autophagy Promotes Tumor Cell Survival and Restricts Necrosis, Inflammation, and Tumorigenesis. Cancer Cell, 10, 51-64. [Google Scholar] [CrossRef] [PubMed]
[23] Tang, F., Wang, Y., Hemmings, B.A., Rüegg, C. and Xue, G. (2018) PKB/Akt-Dependent Regulation of Inflammation in Cancer. Seminars in Cancer Biology, 48, 62-69. [Google Scholar] [CrossRef] [PubMed]
[24] Cravero, J.D., Carlson, C.S., Im, H.J., Yammani, R.R., Long, D. and Loeser, R.F. (2009) Increased Expression of the Akt/PKB Inhibitor TRB3 in Osteoarthritic Chondrocytes Inhibits Insulin-Like Growth Factor 1-Mediated Cell Survival and Proteoglycan Synthesis. Arthritis & Rheumatology, 60, 492-500. [Google Scholar] [CrossRef] [PubMed]
[25] 张风娥, 邵婉珍, 吴翠艳, 郭雄. PI3K/Akt信号通路在大骨节病发生发展中的研究进展[J]. 国外医学(医学地理分册), 2017, 38(1), 85-88.
[26] Sun, K., Luo, J., Guo, J., Yao, X., Jing, X. and Guo, F. (2020) The PI3K/AKT/mTOR Signaling Pathway in Osteoarthritis: A Narrative Review. Osteoarthritis and Cartilage, 28, 400-409. [Google Scholar] [CrossRef] [PubMed]
[27] 邓欢, 吕艺蓁, 刘宣, 肖香, 乔利春, 郭紫薇, 赵妍, 刘家欣, 韩晶. PI3K/AKT信号通路调控骨关节疾病软骨细胞自噬及损伤的机制[J]. 西安交通大学学报(医学版), 2022, 43(2), 309-314.
[28] Nussinov, R., Tsai, C.J. and Jang, H. (2020) Ras Assemblies and Signaling at the Membrane. Current Opinion in Structural Biology, 62, 140-148. [Google Scholar] [CrossRef] [PubMed]
[29] Ning, Y., Wang, X., Lammi, M.J. and Guo, X. (2019) Changes in the NF-κB Signaling Pathway in Juvenile and Adult Patients with Kashin-Beck Disease. Experimental Cell Research, 379, 140-149. [Google Scholar] [CrossRef] [PubMed]
[30] Kma, L. and Baruah, T.J. (2022) The Interplay of ROS and the PI3K/Akt Pathway in Autophagy Regulation. Biotechnology and Applied Biochemistry, 69, 248-264. [Google Scholar] [CrossRef] [PubMed]
[31] Valenti, M.T., Dalle Carbonare, L., Zipeto, D. and Mottes, M. (2021) Control of the Autophagy Pathway in Osteoarthritis: Key Regulators, Therapeutic Targets and Therapeutic Strategies. International Journal of Molecular Sciences, 22, Article 2700. [Google Scholar] [CrossRef] [PubMed]
[32] Tian, Z., Zhang, X. and Sun, M. (2021) Phytochemicals Mediate Autophagy against Osteoarthritis by Maintaining Cartilage Homeostasis. Frontiers in Pharmacology, 12, Article 795058. [Google Scholar] [CrossRef] [PubMed]
[33] Xue, J.F., Shi, Z.M., Zou, J. and Li, X.L. (2017) Inhibition of PI3K/AKT/mTOR Signaling Pathway Promotes Autophagy of Articular Chondrocytes and Attenuates Inflammatory Response in Rats with Osteoarthritis. Biomedicine & Pharmacotherapy, 89, 1252-1261. [Google Scholar] [CrossRef] [PubMed]
[34] Rosenthal, A.K., Gohr, C.M., Mitton-Fitzgerald, E., Grewal, R., Ninomiya, J., Coyne, C.B. and Jackson, W.T. (2015) Autophagy Modulates Articular Cartilage Vesicle Formation in Primary Articular Chondrocytes. Journal of Biological Chemistry, 290, 13028-13038. [Google Scholar] [CrossRef
[35] Lei, S., Zhang, Y., Zhang, K., Li, J. and Liu, L. (2015) Effects of Fluoride on the Expression of Beclin1 and mTOR in Ameloblasts. Cells Tissues Organs, 200, 405-412. [Google Scholar] [CrossRef] [PubMed]