Progress in multi-omics studies of osteoarthritis

Abstract

Osteoarthritis (OA), a ubiquitous degenerative joint disorder, is marked by pain and disability, profoundly impacting patients' quality of life. As the population ages, the global prevalence of OA is escalating. Omics technologies have become instrumental in investigating complex diseases like OA, offering comprehensive insights into its pathogenesis and progression by uncovering disease-specific alterations across genomics, transcriptomics, proteomics, and metabolomics levels. In this review, we systematically analyzed and summarized the application and recent achievements of omics technologies in OA research by scouring relevant literature in databases such as PubMed. These studies have shed light on new potential therapeutic targets and biomarkers, charting fresh avenues for OA diagnosis and treatment. Furthermore, in our discussion, we highlighted the immense potential of spatial omics technologies in unraveling the molecular mechanisms of OA and in the development of novel therapeutic strategies, proposing future research directions and challenges. Collectively, this study encapsulates the pivotal advances in current OA research and prospects for future investigation, providing invaluable references for a deeper understanding and treatment of OA. This review aims to synthesize the recent progress of omics technologies in the realm of OA, aspiring to furnish theoretical foundations and research orientations for more profound studies of OA in the future.

Keywords: Genomics; Omics; Osteoarthritis; Proteomics; Transcriptomics.

Fig. 1

The Role of the Innate Immune System in the Pathogenesis of Osteoarthritis (OA). When joint cartilage or surrounding tissues are injured, endogenous molecules such as damage-associated molecular patterns (DAMPs), are released into the extracellular environment. DAMPs activate innate immune cells, such as macrophages, by binding to pattern recognition receptors (PRRs), thereby triggering a cascade of inflammatory reactions. This leads to the release of cytokines, chemokines, and other inflammatory mediators, resulting in further joint damage and exacerbation of inflammation. Activated immune cells produce pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), which are highly expressed in the synovium and promote inflammatory responses leading to cartilage degradation, joint inflammation, and bone remodeling. Concurrently, chondrocytes are also subjected to cartilage degradation under the influence of matrix metalloproteinases 3 (MMP3) and 13 (MMP13)

Fig. 2

The process of apoptosis in OA. Chronic mechanical stress, pro-inflammatory cytokines such as IL-1β and TNF-α, and ROS can all initiate apoptosis in chondrocytes. Apoptosis primarily occurs through two pathways: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway involves increasing the permeability of the mitochondrial outer membrane, releasing cytochrome c, which binds to Apaf-1 to form the apoptosome, activating caspase-9, and subsequently activating caspase-3/7, leading to cell apoptosis. The extrinsic pathway is mediated by death receptors (such as Fas and TNF receptors), which activate caspase-8, that in turn activates caspase-3/7, leading to cell apoptosis

Fig. 3

The process of pyroptosis in OA. Inflammatory factors such as IL-1β and TNF-α can activate autophagy to form autophagosomes. AMPK signaling pathways initiate autophagy by activating the ULK1 complex. mTOR signaling pathways can inhibit autophagy

Fig. 4

The process of pyroptosis in OA. Mechanical stress, injury and infection can activate the NLRP3 inflammasome. Once activated, the NLRP3 inflammasome recruits ASC (apoptosis-associated speck-like protein containing a pyrin domain), forming an inflammasome complex that promotes the recruitment and self-cleavage of procaspase-1, activating caspase-1. Activated caspase-1 cleaves the pro-inflammatory cytokine precursors pro-IL-1β and pro-IL-18, generating active IL-1β and IL-18. Additionally, caspase-1 cleaves gasdermin D (GSDMD), whose N-terminal fragment forms a pore-forming protein, leading to cell membrane rupture and the release of pro-inflammatory cytokines such as IL-1β and IL-18. These molecules activate adjacent cells and the immune system, triggering a strong inflammatory response that leads to pyroptosis