Ribosome dysfunction in osteoarthritis

Abstract

Purpose of review Translation of genetic information encoded within mRNA molecules by ribosomes into proteins is a key part of the central dogma of molecular biology. Despite the central position of the ribosome in the translation of proteins, and considering the major proteomic changes that occur in the joint during osteoarthritis development and progression, the ribosome has received very limited attention as driver of osteoarthritis pathogenesis. Recent findings We provide an overview of the limited literature regarding this developing topic for the osteoarthritis field. Recent key findings that connect ribosome biogenesis and activity with osteoarthritis include: ribosomal RNA transcription, processing and maturation, ribosomal protein expression, protein translation capacity and preferential translation. Summary The ribosome as the central cellular protein synthesis hub is largely neglected in osteoarthritis research. Findings included in this review reveal that in osteoarthritis, ribosome aberrations have been found from early-stage ribosome biogenesis, through ribosome build-up and maturation, up to preferential translation. Classically, osteoarthritis has been explained as an imbalance between joint tissue anabolism and catabolism. We postulate that osteoarthritis can be interpreted as an acquired ribosomopathy. This hypothesis fine-tunes the dogmatic anabolism/katabolism point-of-view, and may provide novel molecular opportunities for the development of osteoarthritis disease-modifying treatments.

Small non-coding RNA landscape of extracellular vesicles from a post-traumatic model of equine osteoarthritis

“…We also investigated the changes in snoRNAs. From our previous study, we have known that snoRNAs have an important role in joint homeostasis ( 93 ), mouse joint ageing ( 17 ), chondrogenic differentiation ( 94 ), cartilage ageing ( 15 ), OA ( 6 , 7 ), and early OA SF ( 8 ). Interestingly, in the plasma, we found that 82% of DE snoRNAs in the plasma were also identified in ageing/OA human cartilage study ( 7 ), including Snord113/114, snord15, snord30, snord32/33, snord46, snord58, snord62, snord66, snord69, snord74, snord75, and U3.…”

“…Overall, the changes in snoRNAs in EVs in both the plasma and the SF provide an insight into their role in the pathogenesis of OA, as traditionally OA has been defined as an imbalance between joint anabolism and catabolism. With our increasing evidence that it is an acquired ribosomopathy ( 93 ), there is a potential role for EV-derived snoRNAs to contribute to OA pathogenesis via its cell communication role. We are currently studying sncRNA cross-talk in joint cells to shed more light on this hypothesis ( 99 ).…”

Small non-coding RNA landscape of extracellular vesicles from a post-traumatic model of equine osteoarthritis

“…Overall the changes in snoRNAs in EVs in both plasma and SF provide insight into their role in the pathogenesis of OA as traditionally OA has been defined as an imbalance between joint anabolism/catabolism. With our increasing evidence that it is an acquired ribosomopathy (84), there is a potential role for EV-derived snoRNAs to contribute to OA pathogenesis via its cell communication role. We are currently studying sncRNA cross talk in joint cells to shed more light on this hypothesis (90).…”

“…We also investigated the changes in snoRNAs. From our previous work we know snoRNAs have an important role in joint homeostasis (84), in mouse joint ageing (16), in chondrogenic differentiation (85), in cartilage ageing (14), in OA (6, 7) and in early OA SF (8). Interestingly in plasma we found that 82% of the snoRNAs DE in plasma were also identified in ageing/OA human cartilage study (7), including Snord113/114, snord15, snord30, snord32/33, snord46, snord58, snord62, snord66, snord69, snord74, snord75 and U3.…”

Identification of the genetic central dogma in osteogenic differentiation of MSCs by osteoinductive medium from transcriptional data sets

“… 9 To date, the concepts of splicing and ribonucleic acid (RNA) editing consummate the GCD; meanwhile, entire information on DNA–RNA–protein processes is included. 10 , 11 GCD makes different contributions to many physical and pathological processes, including oncogenesis, 12 mechanical stress on human cells, 13 osteoarthritis, 14 and so on. However, the roles of GCD in the differentiation of stem cells remain unknown.…”