scholarly journals Heat shock proteins - participants in osteoarthrosis pathogenesis

2016 ◽  
Vol 97 (5) ◽  
pp. 744-749 ◽  
Author(s):  
M A Kabalyk ◽  
B I Gel’tser ◽  
A L Osipov ◽  
M F Fadeev

Osteoarthrosis is a disease that affects all tissues of synovial joints, resulting in chronic pain and often a need for replacement. The high prevalence and the lack of reliable conservative approaches impose significant economic sanctions on most economies in the world. Currently the mechanisms of osteoarthrosis progression have been well studied. At the same time, the known pathogenetic concepts do not allow to define reliable targets of conservative treatment. There is a clear need for searching alternative concepts, which will help to expand the understanding of the pathogenesis and identify ways to address therapeutic issues. Heat shock proteins (chaperones) are involved in intra- and extracellular signaling in the pathogenesis of many diseases. The aim of this review is to analyze the current state of the problem of studying the role of heat shock proteins in the pathogenesis of osteoarthrosis. The review considers the fundamental aspects of the activation and functioning of chaperones, experience of studying chondrocyte heat shock proteins is described, issues of programmed cell death mechanisms are mentioned, scheme of shaperone activity in osteoarthrosis is illustrated. The role of heat shock proteins from the perspectives of reparation and alteration carried out in the articular cartilage is described, the prospects for further clarification of their role in the pathogenesis of osteoarthrosis are identified. The role of two key molecules - protein with molecular weight of 70 kD and a small molecule with molecular weight of 27 kD, is emphasized. Heat shock proteins are of fundamental and applicative interest from the perspective of their participation in the key ways of osteoarthrosis pathogenesis and phenomena (oxidative, microcrystalline, hydrodynamical, stress, aging, etc.). Further study of heat shock proteins will allow to significantly expand the knowledge of osteoarthrosis and to identify ways of targeted therapy.

2021 ◽  
Author(s):  
Ruben Bulkescher ◽  
Thomas Fleming ◽  
Claus Rodemer ◽  
Rebekka Medert ◽  
Marc Freichel ◽  
...  

Increased metabolic flux produces potentially harmful side-products, such as reactive dicarbonyl and oxygen species. The reactive dicarbonly methylglyoxal (MG) can impair oxidative capacity, which is downregulated in type 2 diabetes. Heat shock proteins (HSPs) of subfamily A (Hsp70s) promote ATP-dependent processing of damaged proteins during MG exposure which also involve mitochondrial proteins. Since the protection of mitochondrial proteins could promote higher production of reactive metabolites due to increased substrate flux, tight regulation of HspA-mediated protein handling is important. We hypothesized that stress-inducible HspAs (HspA1A/HspA1B) are pivotal for maintaining mitochondrial biogenesis during acute MG-stress. To analyze the role of stress-inducible HspA1A/HspA1B for maintenance of mitochondrial homeostasis during acute MG exposure, we knocked out HSPA1A/HSPA1B in mouse endothelial cells. HSPA1A/HSPA1B KO cells showed upregulation of the mitochondrial chaperones HspA9 (mitochondrial Hsp70/mortalin) and HspD1 (Hsp60) as well as induction of mitochondrial biogenesis upon MG exposure. Increased mitochondrial biogenesis was reflected by elevated mitochondrial branching, total count and area as well as by upregulation of mitochondrial proteins and corresponding transcription factors. Our findings suggest that mitochondrial HspA9 and HspD1 promote mitochondrial biogenesis during acute MG stress, which is counterregulated by HspA1A/HspA1B to prevent mitochondrial overstimulation and to maintain balanced oxidative capacity under metabolic stress conditions. These data support an important role of HSPs in MG-induced hormesis.


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