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Phosphorylation of KRT8 (keratin 8) by excessive mechanical load-activated PKN (protein kinase N) impairs autophagosome initiation and contributes to disc degeneration
This study validates a protective role of Krt8 during overloading-induced IDD and demonstrates that targeting overloading activation of PKNs could be a novel and effective approach to mechano stress-induced pathologies with a wider window of therapeutic opportunity.Abbreviations: AAV: adeno-associated virus; AF: anulus fibrosus; ANOVA: analysis of variance; ATG: autophagy related; BSA: bovine serum albumin; cDNA: complementary deoxyribonucleic acid; CEP: cartilaginous endplates; CHX: cycloheximide; cKO: conditional knockout; Cor: coronal plane; CT: computed tomography; Cy: coccygeal vertebra; D: aspartic acid; DEG: differe...
Source: Autophagy - March 10, 2023 Category: Cytology Authors: Di Wang Qiliang Shang Jianxin Mao Chu Gao Jie Wang Dong Wang Han Wang Haoruo Jia Pandi Peng Mu Du Zhuojing Luo Liu Yang Source Type: research

Caspase 3 Silencing Inhibits Biomechanical Overload-Induced Intervertebral Disk Degeneration.
Abstract Intervertebral disk (IVD) degeneration causes debilitating low back pain in much of the worldwide population. No efficient treatment exists because of an unclear pathogenesis. One characteristic event early in such degeneration is the apoptosis of nucleus pulposus (NP) cells embedded in IVDs. Excessive biomechanical loading may also be a major etiology of IVD degeneration. The present study used in vitro and in vivo models of compressive loading to elucidate the underlying mechanism of IVD degeneration. In addition, we investigated whether the inhibition of apoptosis is a potential clinical therapeutic ...
Source: The American Journal of Pathology - January 2, 2014 Category: Pathology Authors: Yamada K, Sudo H, Iwasaki K, Sasaki N, Higashi H, Kameda Y, Ito M, Takahata M, Abumi K, Minami A, Iwasaki N Tags: Am J Pathol Source Type: research