scholarly journals The Role of Chondrocyte Hypertrophy and Senescence in Osteoarthritis Initiation and Progression

2020 ◽  
Vol 21 (7) ◽  
pp. 2358 ◽  
Author(s):  
Yeri Alice Rim ◽  
Yoojun Nam ◽  
Ji Hyeon Ju
Keyword(s):  
Adult Population ◽  
Cartilage Damage ◽  
Natural Process ◽  
Joint Disease ◽  
Endochondral Bone Formation ◽  
Potential Therapeutic Target ◽  
Endochondral Bone ◽  
Chondrocyte Hypertrophy ◽  
Age Related

Osteoarthritis (OA) is the most common joint disease that causes pain and disability in the adult population. OA is primarily caused by trauma induced by an external force or by age-related cartilage damage. Chondrocyte hypertrophy or chondrocyte senescence is thought to play a role in the initiation and progression of OA. Although chondrocyte hypertrophy and cell death are both crucial steps during the natural process of endochondral bone formation, the abnormal activation of these two processes after injury or during aging seems to accelerate the progression of OA. However, the exact mechanisms of OA progression and these two processes remain poorly understood. Chondrocyte senescence and hypertrophy during OA share various markers and processes. In this study, we reviewed the changes that occur during chondrocyte hypertrophy or senescence in OA and the attempts that were made to regulate them. Regulation of hypertrophic or senescent chondrocytes might be a potential therapeutic target to slow down or stop OA progression; thus, a better understanding of the processes is required for management.

scholarly journals The role of histone deacetylase 4 during chondrocyte hypertrophy and endochondral bone development

2020 ◽  
Vol 9 (2) ◽  
pp. 82-89 ◽  
Author(s):  
Zhi Chen ◽  
Zhiwei Zhang ◽  
Li Guo ◽  
Xiaochun Wei ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Bone Development ◽  
Chromatin Condensation ◽  
Negative Regulator ◽  
Endochondral Bone Formation ◽  
Endochondral Bone ◽  
Chondrocyte Hypertrophy ◽  
Histone Deacetylase 4

Chondrocyte hypertrophy represents a crucial turning point during endochondral bone development. This process is tightly regulated by various factors, constituting a regulatory network that maintains normal bone development. Histone deacetylase 4 (HDAC4) is the most well-characterized member of the HDAC class IIa family and participates in different signalling networks during development in various tissues by promoting chromatin condensation and transcriptional repression. Studies have reported that HDAC4-null mice display premature ossification of developing bones due to ectopic and early-onset chondrocyte hypertrophy. Overexpression of HDAC4 in proliferating chondrocytes inhibits hypertrophy and ossification of developing bones, which suggests that HDAC4, as a negative regulator, is involved in the network regulating chondrocyte hypertrophy. Overall, HDAC4 plays a key role during bone development and disease. Thus, understanding the role of HDAC4 during chondrocyte hypertrophy and endochondral bone formation and its features regarding the structure, function, and regulation of this process will not only provide new insight into the mechanisms by which HDAC4 is involved in chondrocyte hypertrophy and endochondral bone development, but will also create a platform for developing a therapeutic strategy for related diseases. Cite this article: Bone Joint Res. 2020;9(2):82–89.

scholarly journals Rhoifolin Ameliorates Osteoarthritis via Regulating Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiyuan Yan ◽  
Bowei Ni ◽  
Gaohong Sheng ◽  
Yingchi Zhang ◽  
Yifan Xiao ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Joint Disease ◽  
Signal Pathways ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Age Related ◽  
Anti Inflammatory

Osteoarthritis (OA) is a common age-related joint disease. Its development has been generally thought to be associated with inflammation and autophagy. Rhoifolin (ROF), a flavanone extracted from Rhus succedanea, has exhibited prominent anti-oxidative and anti-inflammatory properties in several diseases. However the exact role of ROF in OA remains unclear. Here, we investigated the therapeutic effects as well as the underlying mechanism of ROF on rat OA. Our results indicated that ROF could significantly alleviate the IL-1β–induced inflammatory responses, cartilage degradation, and autophagy downregulation in rat chondrocytes. Moreover, administration of autophagy inhibitor 3-methyladenine (3-MA) could reverse the anti-inflammatory and anti-cartilage degradation effects of ROF. Furthermore, P38/JNK and PI3K/AKT/mTOR signal pathways were involved in the protective effects of ROF. In vivo, intra-articular injection of ROF could notably ameliorate the cartilage damage in rat OA model. In conclusion, our work elucidated that ROF ameliorated rat OA via regulating autophagy, indicating the potential role of ROF in OA therapy.

scholarly journals Selonsertib Alleviates the Progression of Rat Osteoarthritis: An in vitro and in vivo Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiyuan Yan ◽  
Yingchi Zhang ◽  
Gaohong Sheng ◽  
Bowei Ni ◽  
Yifan Xiao ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Therapeutic Effects ◽  
Exact Role

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1β-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.

scholarly journals Autophagy and Age-Related Eye Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xue Yang ◽  
Xinan Pan ◽  
Xiaorui Zhao ◽  
Jin Luo ◽  
Mingpu Xu ◽  
...  
Keyword(s):  
Eye Diseases ◽  
Regulatory Function ◽  
Ocular Diseases ◽  
Potential Therapeutic Target ◽  
Age Related ◽  
Different Types ◽  
Survival And Development ◽  
Catabolic Process

Background. Autophagy is a catabolic process that depends on the lysosome. It is usually used to maintain cellular homeostasis, survival and development by degrading abnormal substances and dysfunctional organelles, especially when the cell is exposed to starvation or other stresses. Increasing studies have reported that autophagy is associated with various eye diseases, of which aging is one of the important factors. Objective. To summarize the functional and regulatory role of autophagy in ocular diseases with aging, and discuss the possibility of autophagy-targeted therapy in age-related diseases. Methods. PubMed searches were performed to identify relevant articles published mostly in the last 5 years. The key words were used to retrieve including “autophagy”, “aging”, “oxidative stress AND autophagy”, “dry eye AND autophagy”, “corneal disease AND autophagy”, “glaucoma AND autophagy”, “cataract AND autophagy”, “AMD AND autophagy”, “cardiovascular diseases AND autophagy”, “diabetes AND autophagy”. After being classified and assessed, the most relevant full texts in English were chosen. Results. Apart from review articles, more than two research articles for each age-related eye diseases related to autophagy were retrieved. We only included the most relevant and recent studies for summary and discussion. Conclusion. Autophagy has both protective and detrimental effects on the progress of age-related eye diseases. Different types of studies based on certain situations in vitro showed distinct results, which do not necessarily coincide with the actual situation in human bodies completely. It means the exact role and regulatory function of autophagy in ocular diseases remains largely unknown. Although autophagy as a potential therapeutic target has been proposed, many problems still need to be solved before it applies to clinical practice.

scholarly journals A review of the multifunctionality of angiopoietin-like 4 in eye disease

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Xinyue Yang ◽  
Yan Cheng ◽  
Guanfang Su
Keyword(s):  
Molecular Mechanisms ◽  
Age Related Macular Degeneration ◽  
Eye Disease ◽  
Future Research ◽  
Potential Therapeutic Target ◽  
Vein Occlusion ◽  
Age Related ◽  
Functional Mechanisms ◽  
Multifunctional Cytokine

Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine regulating vascular permeability, angiogenesis, and inflammation. Dysregulations in these responses contribute to the pathogenesis of ischemic retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion, and sickle cell retinopathy (SCR). However, the role of ANGPTL4 in these diseases remains controversial. Here, we summarize the functional mechanisms of ANGPTL4 in several diseases. We highlight original studies that provide detailed data about the mechanisms of action for ANGPTL4, its applications as a diagnostic or prognostic biomarker, and its use as a potential therapeutic target. Taken together, the discussions in this review will help us gain a better understanding of the molecular mechanisms by which ANGPTL4 functions in eye disease and will provide directions for future research.

The role of Akt1 in terminal stages of endochondral bone formation: Angiogenesis and ossification

Bone ◽  
2009 ◽  
Vol 45 (6) ◽  
pp. 1133-1145 ◽  
Author(s):  
Veronica Ulici ◽  
Katie D. Hoenselaar ◽  
Hanga Agoston ◽  
David D. McErlain ◽  
Joseph Umoh ◽  
...  
Keyword(s):  
Bone Formation ◽  
Endochondral Bone Formation ◽  
Endochondral Bone

scholarly journals Expression and Role of IL-1β Signaling in Chondrocytes Associated with Retinoid Signaling during Fracture Healing

2020 ◽  
Vol 21 (7) ◽  
pp. 2365 ◽  
Author(s):  
Tsuyoshi Shimo ◽  
Hiroaki Takebe ◽  
Tatsuo Okui ◽  
Yuki Kunisada ◽  
Soichiro Ibaragi ◽  
...  
Keyword(s):  
Bone Formation ◽  
Fracture Healing ◽  
P38 Mapk ◽  
Inverse Agonist ◽  
Endochondral Bone Formation ◽  
Dependent Manner ◽  
Retinoid Receptor ◽  
Endochondral Bone ◽  
Inverse Agonists

The process of fracture healing consists of an inflammatory reaction and cartilage and bone tissue reconstruction. The inflammatory cytokine interleukin-1β (IL-1β) signal is an important major factor in fracture healing, whereas its relevance to retinoid receptor (an RAR inverse agonist, which promotes endochondral bone formation) remains unclear. Herein, we investigated the expressions of IL-1β and retinoic acid receptor gamma (RARγ) in a rat fracture model and the effects of IL-1β in the presence of one of several RAR inverse agonists on chondrocytes. An immunohistochemical analysis revealed that IL-1β and RARγ were expressed in chondrocytes at the fracture site in the rat ribs on day 7 post-fracture. In chondrogenic ATDC5 cells, IL-1β decreases the levels of aggrecan and type II collagen but significantly increased the metalloproteinase-13 (Mmp13) mRNA by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. An RAR inverse agonist (AGN194310) inhibited IL-1β-stimulated Mmp13 and Ccn2 mRNA in a dose-dependent manner. Phosphorylated extracellular signal regulated-kinases (pERK1/2) and p-p38 mitogen-activated protein kinase (MAPK) were increased time-dependently by IL-1β treatment, and the IL-1β-induced p-p38 MAPK was inhibited by AGN194310. Experimental p38 inhibition led to a drop in the IL-1β-stimulated expressions of Mmp13 and Ccn2 mRNA. MMP13, CCN2, and p-p38 MAPK were expressed in hypertrophic chondrocytes near the invaded vascular endothelial cells. As a whole, these results point to role of the IL-1β via p38 MAPK as important signaling in the regulation of the endochondral bone formation in fracture healing, and to the actions of RAR inverse agonists as potentially relevant modulators of this process.

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