cartilage homeostasis
Recently Published Documents


TOTAL DOCUMENTS

143
(FIVE YEARS 52)

H-INDEX

27
(FIVE YEARS 5)

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Sujeong Park ◽  
In-Jeoung Baek ◽  
Ji Hyun Ryu ◽  
Churl-Hong Chun ◽  
Eun-Jung Jin

AbstractHere, in Ppara−/− mice, we found that an increased DNL stimulated the cartilage degradation and identified ACOT12 as a key regulatory factor. Suppressed level of ACOT12 was observed in cartilages of OA patient and OA-induced animal. To determine the role and association of ACOT12 in the OA pathogenesis, we generated Acot12 knockout (KO) (Acot12−/−) mice using RNA-guided endonuclease. Acot12−/− mice displayed the severe cartilage degradation with the stimulation of matrix MMPs and chondrocyte apoptosis through the accumulation of acetyl CoA. Delivery of acetyl CoA-conjugated chitosan complex into cartilage stimulated DNL and cartilage degradation. Moreover, restoration of ACOT12 into human OA chondrocytes and OA-induced mouse cartilage effectively rescued the pathophysiological features of OA by regulating DNL. Taken together, our study suggested ACOT12 as a novel regulatory factor in maintaining cartilage homeostasis and targeting ACOT12 could contribute to developing a new therapeutic strategy for OA.


Author(s):  
Mylène Zarka ◽  
Eric Haÿ ◽  
Martine Cohen-Solal

YAP and TAZ were initially described as the main regulators of organ growth during development and more recently implicated in bone biology. YAP and TAZ are regulated by mechanical and cytoskeletal cues that lead to the control of cell fate in response to the cellular microenvironment. The mechanical component represents a major signal for bone tissue adaptation and remodelling, so YAP/TAZ contributes significantly in bone and cartilage homeostasis. Recently, mice and cellular models have been developed to investigate the precise roles of YAP/TAZ in bone and cartilage cells, and which appear to be crucial. This review provides an overview of YAP/TAZ regulation and function, notably providing new insights into the role of YAP/TAZ in bone biology.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zheng Tian ◽  
Xinan Zhang ◽  
Mingli Sun

Osteoarthritis (OA) is a common degenerative joint disease and is a leading cause of disability and reduced quality of life worldwide. There are currently no clinical treatments that can stop or slow down OA. Drugs have pain-relieving effects, but they do not slow down the course of OA and their long-term use can lead to serious side effects. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Autophagy is an intracellular protective mechanism, and targeting autophagy-related pathways has been found to prevent and treat various diseases. Attenuation of the autophagic pathway has now been found to disrupt cartilage homeostasis and plays an important role in the development of OA. Therefore, modulation of autophagic signaling pathways mediating cartilage homeostasis has been considered as a potential therapeutic option for OA. Phytochemicals are active ingredients from plants that have recently been found to reduce inflammatory factor levels in cartilage as well as attenuate chondrocyte apoptosis by modulating autophagy-related signaling pathways, which are not only widely available but also have the potential to alleviate the symptoms of OA. We reviewed preclinical studies and clinical studies of phytochemicals mediating autophagy to regulate cartilage homeostasis for the treatment of OA. The results suggest that phytochemicals derived from plant extracts can target relevant autophagic pathways as complementary and alternative agents for the treatment of OA if subjected to rigorous clinical trials and pharmacological tests.


Author(s):  
Yanxi Liu ◽  
Karan M. Shah ◽  
Jian Luo

Articular cartilage is an avascular tissue, with limited ability to repair and self-renew. Defects in articular cartilage can induce debilitating degenerative joint diseases such as osteoarthritis. Currently, clinical treatments have limited ability to repair, for they often result in the formation of mechanically inferior cartilage. In this review, we discuss the factors that affect cartilage homeostasis and function, and describe the emerging regenerative approaches that are informing the future treatment options.


Author(s):  
Zongmian Song ◽  
Yusheng Li ◽  
Chunfeng Shang ◽  
Guowei Shang ◽  
Hongwei Kou ◽  
...  

When suffering from osteoarthritis (OA), articular cartilage homeostasis is out of balance and the living quality declines. The treatment of knee OA has always been an unsolved problem in the world. At present, symptomatic treatment is mainly adopted for OA. Drug therapy is mainly used to relieve pain symptoms, but often accompanied with adverse reactions; surgical treatment involves the problem of poor integration between the repaired or transplanted tissues and the natural cartilage, leading to the failure of repair. Biotherapy which aims to promote cartilage in situ regeneration and to restore endochondral homeostasis is expected to be an effective method for the prevention and treatment of OA. Disease-modifying osteoarthritis drugs (DMOADs) are intended for targeted treatment of OA. The DMOADs prevent excessive destruction of articular cartilage through anti-catabolism and stimulate tissue regeneration via excitoanabolic effects. Sprifermin (recombinant human FGF18, rhFGF18) is an effective DMOAD, which can not only promote the proliferation of articular chondrocyte and the synthesis of extracellular matrix, increase the thickness of cartilage in a dose-dependent manner, but also inhibit the activity of proteolytic enzymes and remarkedly slow down the degeneration of cartilage. This paper reviews the unique advantages of Sprifermin in repairing cartilage injury and improving cartilage homeostasis, aiming to provide an important strategy for the effective prevention and treatment of cartilage injury-related diseases.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yoshiaki Ito ◽  
Tokio Matsuzaki ◽  
Fumiaki Ayabe ◽  
Sho Mokuda ◽  
Ryota Kurimoto ◽  
...  

AbstractOsteoarthritis (OA), the most common aging-related joint disease, is caused by an imbalance between extracellular matrix synthesis and degradation. Here, we discover that both strands of microRNA-455 (miR-455), -5p and -3p, are up-regulated by Sox9, an essential transcription factor for cartilage differentiation and function. Both miR-455-5p and -3p are highly expressed in human chondrocytes from normal articular cartilage and in mouse primary chondrocytes. We generate miR-455 knockout mice, and find that cartilage degeneration mimicking OA and elevated expression of cartilage degeneration-related genes are observed at 6-months-old. Using a cell-based miRNA target screening system, we identify hypoxia-inducible factor-2α (HIF-2α), a catabolic factor for cartilage homeostasis, as a direct target of both miR-455-5p and -3p. In addition, overexpression of both miR-455-5p and -3p protect cartilage degeneration in a mouse OA model, demonstrating their potential therapeutic value. Furthermore, knockdown of HIF-2α in 6-month-old miR-455 knockout cartilage rescues the elevated expression of cartilage degeneration-related genes. These data demonstrate that both strands of a miRNA target the same gene to regulate articular cartilage homeostasis.


Author(s):  
Hui Chen ◽  
Xiao-Ning Tan ◽  
Shi Hu ◽  
Ren-Qin Liu ◽  
Li-Hong Peng ◽  
...  

Cartilage is a kind of connective tissue that buffers pressure and is essential to protect joint movement. It is difficult to self-recover once cartilage is damaged due to the lack of blood vessels, lymph, and nerve tissues. Repair of cartilage injury is mainly achieved by stimulating chondrocyte proliferation and extracellular matrix (ECM) synthesis. Cartilage homeostasis involves the regulation of multiple growth factors and the transduction of cellular signals. It is a very complicated process that has not been elucidated in detail. In this review, we summarized a variety of signaling molecules related to chondrocytes function. Especially, we described the correlation between chondrocyte-specific regulatory factors and cell signaling molecules. It has potential significance for guiding the treatment of cartilage injury.


2021 ◽  
Vol 22 (11) ◽  
pp. 5711
Author(s):  
Julian Zacharjasz ◽  
Anna M. Mleczko ◽  
Paweł Bąkowski ◽  
Tomasz Piontek ◽  
Kamilla Bąkowska-Żywicka

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world's population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.


2021 ◽  
Author(s):  
Hope D Welhaven ◽  
Carley N McCutchen ◽  
Ronald K June

Mechanotransduction is a biological phenomenon where mechanical stimuli are converted to biochemical responses. A model system for studying mechanotransduction are the chondrocytes of articular cartilage. Breakdown of this tissue results in decreased mobility, increased pain, and reduced quality of life. Either disuse or overloading can disrupt cartilage homeostasis, but physiological cyclical loading promotes cartilage homeostasis. To model this, we exposed SW1353 cells to cyclical mechanical stimuli, shear and compression, for different durations of time (15 and 30 min). By utilizing liquid chromatography-mass spectroscopy (LC-MS), metabolomic profiles were generated detailing metabolite features and biological pathways that are altered in response to mechanical stimulation. In total, 1,457 metabolite features were detected. Statistical analyses identified several pathways of interest. Taken together, differences between experimental groups were associated with inflammatory pathways, lipid metabolism, beta-oxidation, central energy metabolism, and amino acid production. These findings expand our understanding of chondrocyte mechanotransduction under varying loading conditions and time periods.


Bone Reports ◽  
2021 ◽  
Vol 14 ◽  
pp. 100917
Author(s):  
Jana Riegger-Koch ◽  
Sai Pulasani ◽  
Rolf E. Brenner

Sign in / Sign up

Export Citation Format

Share Document