scholarly journals Sprifermin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-Related Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Zongmian Song ◽  
Yusheng Li ◽  
Chunfeng Shang ◽  
Guowei Shang ◽  
Hongwei Kou ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Proteolytic Enzymes ◽  
Symptomatic Treatment ◽  
Cartilage Injury ◽  
Dependent Manner ◽  
Articular Chondrocyte ◽  
Effective Prevention ◽  
Knee Oa ◽  
Cartilage Homeostasis ◽  
Prevention And Treatment

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.

scholarly journals FoxO1 is a crucial mediator of TGF-β/TAK1 signaling and protects against osteoarthritis by maintaining articular cartilage homeostasis

2020 ◽  
Vol 117 (48) ◽  
pp. 30488-30497
Author(s):  
Cuicui Wang ◽  
Jie Shen ◽  
Jun Ying ◽  
Ding Xiao ◽  
Regis J. O’Keefe
Keyword(s):  
Articular Cartilage ◽  
Regulatory Networks ◽  
Transforming Growth Factor ◽  
Cartilage Tissue ◽  
Ligament Injury ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Articular Chondrocyte ◽  
Gene Expressions ◽  
Cartilage Homeostasis

Transforming growth factor-β (TGF-β) signaling is a critical regulator for articular cartilage tissue maintenance and chondrocyte homeostasis. Nonetheless, the regulatory networks and downstream signaling pathways that govern the chondroprotective function of TGF-β in the context of osteoarthritis (OA) are not fully defined. Recent studies reveal that mice with postnatal deletion of triple forkhead box class Os (FoxOs) (1, 3, and 4) spontaneously develop OA-like pathologies. The OA phenotype largely recapitulates that observed in mice with loss of TGF-βR2. In the present study, we investigated the role of FoxOs as downstream mediators of TGF-β signaling and define their role in articular cartilage homeostasis. Among the three FoxOs (1, 3, and 4), TGF-β signaling exclusively regulates FoxO1 in a TGF-β activated kinase 1 (TAK1)-dependent manner. Furthermore, FoxO1 was genetically ablated in mice in a tissue-specific manner in articular cartilage or overexpressed in adult cartilage immediately followed by meniscal/ligament injury (MLI). Histological and microcomputed tomography (micro-CT) analyses demonstrated that loss of FoxO1 postnatally in articular cartilage leads to OA-like pathologies, and gain of FoxO1 in adult cartilage has both preventative and therapeutic effects on surgically induced OA. Mechanistically, FoxO1 was found to maintain articular chondrocyte homeostasis through induction of anabolic and autophagy-related gene expressions. Importantly, overexpression of FoxO1 markedly rescued the OA phenotypes caused by deficiency in TGF-β signaling in chondrocytes. Our study identifies that TGF-β/TAK1-FoxO1 is a key signaling cascade in regulation of articular cartilage autophagy and homeostasis and is a potentially important therapeutic target for OA-like joint diseases.

MAPK: A Key Player in the Development and Progression of Stroke

2020 ◽  
Vol 19 (4) ◽  
pp. 248-256
Author(s):  
Yangmin Zheng ◽  
Ziping Han ◽  
Haiping Zhao ◽  
Yumin Luo
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Complex Disease ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Effective Prevention ◽  
Prevention And Treatment ◽  
Different Cell Types

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.

scholarly journals Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments

2021 ◽  
Vol 22 (11) ◽  
pp. 5711
Author(s):  
Julian Zacharjasz ◽  
Anna M. Mleczko ◽  
Paweł Bąkowski ◽  
Tomasz Piontek ◽  
Kamilla Bąkowska-Żywicka
Keyword(s):  
Knee Osteoarthritis ◽  
Noncoding Rnas ◽  
Pathological Process ◽  
Joint Disease ◽  
Limited Information ◽  
Genetic Changes ◽  
Small Noncoding Rnas ◽  
Knee Oa ◽  
Cartilage Homeostasis

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.

Staying alive: A 21st century agenda for mental health, child protection and forensic services

2021 ◽  
pp. 263440412110078
Author(s):  
Patricia M Crittenden ◽  
Andrea Landini ◽  
Susan J Spieker
Keyword(s):  
Mental Health ◽  
Mental Health Professionals ◽  
Child Protection ◽  
Mental Health Treatment ◽  
Developmental Process ◽  
Diagnostic Methods ◽  
Effective Prevention ◽  
Common Basis ◽  
Prevention And Treatment ◽  
Protective Strategies

Mental health treatment, child protection and forensic services for criminality need major reorganisation in conceptualisation and service provision. This need results from the failure of current diagnostic methods, administrative organisations and treatment approaches to reduce the prevalence of mental illness, child maltreatment or criminal behaviour. We propose that defining these problems as individual deficits and responding to them by category of harm (to self, progeny and others, respectively) stands in the way of effective prevention and treatment. We address four topics: (1) the common basis of all of these problems in unprotected and uncomforted exposure to danger, (2) the developmental process of psychological maladaptation that occurs interpersonally in endangered families, (3) the behavioural expression of psychological development as protective strategies that can be adaptive or maladaptive, depending upon the context in which they are used, and (4) proposals for systemic change that could improve prevention and treatment. These proposals include using functional formulations to guide treatment planning, single portal entry to assessment and services, integrated universal transdisciplinary training followed by specialisation for all mental health professionals, delivering customised treatment through transitional attachment relationships and consolidating disparate disciplines in ‘departments of human adaptation’.

scholarly journals Prostaglandin E2and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis

2009 ◽  
Vol 60 (2) ◽  
pp. 513-523 ◽  
Author(s):  
Xin Li ◽  
Michael Ellman ◽  
Prasuna Muddasani ◽  
James H.-C. Wang ◽  
Gabriella Cs-Szabo ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Ep Receptors ◽  
Human Adult ◽  
Cartilage Homeostasis

Adult human chondrocytes cultured in alginate form a matrix similar to native human articular cartilage

1996 ◽  
Vol 271 (3) ◽  
pp. C742-C752 ◽  
Author(s):  
H. J. Hauselmann ◽  
K. Masuda ◽  
E. B. Hunziker ◽  
M. Neidhart ◽  
S. S. Mok ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cell Sorting ◽  
Proteolytic Enzymes ◽  
Alginate Beads ◽  
Human Chondrocytes ◽  
Human Articular Cartilage ◽  
Adult Human ◽  
The Matrix ◽  
Matrix Compartment ◽  
Associated Matrix

The matrix formed by adult human chondrocytes in alginate beads is composed of two compartments: a thin rim of cell-associated matrix that corresponds to the pericellular and territorial matrix of articular cartilage and a more abundant further-removed matrix, the equivalent of the interterritorial matrix in the tissue. On day 30 of culture, the relative and absolute volumes occupied by the cells and each of the two matrix compartments in the beads were nearly identical to those in native articular cartilage. Furthermore, the concentration of aggrecan in the cell-associated matrix was similar to that in adult human articular cartilage and was approximately 40-fold higher than in the further removed matrix compartment. Fluorescence-activated cell sorting revealed that the cell-associated matrix was built on the cell membrane in part via interactions between hyaluronic acid and CD44-like receptors. Approximately 25% of the aggrecan molecules synthesized by the chondrocytes during a 4-h pulse in the presence of [35S]sulfate on day 9 of culture were retained in the cell-associated matrix where they turned over with a half-life (t1/2) = 29 days. Most [35S]aggrecan molecules reached the further removed matrix compartment where they turned over much more slowly (t1/2 > 100 days). These results add support to the contention that aggrecan molecules residing in the pericellular and territorial areas of the adult human articular cartilage matrix are more susceptible to degradation by proteolytic enzymes synthesized by the chondrocytes than those that inhabit the interterritorial areas further removed from the cells.

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