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Osteoarthritis (OA) is a debilitating degenerative disease affecting multiple joint tissues, including cartilage, bone, synovium, and adipose tissues. OA presents diverse clinical phenotypes and distinct molecular endotypes, including inflammatory, metabolic, mechanical, genetic, and synovial variants. Consequently, innovative technologies are needed to support the development of effective diagnostic and precision therapeutic approaches. Traditional analysis of bulk OA tissue extracts has limitations due to technical constraints, causing challenges in the differentiation between various physiological and pathological phenotypes in joint tissues. This issue has led to standardization difficulties and hindered the success of clinical trials. Gaining insights into the spatial variations of the cellular and molecular structures in OA tissues, encompassing DNA, RNA, metabolites, and proteins, as well as their chemical properties, elemental composition, and mechanical attributes, can contribute to a more comprehensive understanding of the disease subtypes. Spatially resolved biology enables biologists to investigate cells within the context of their tissue microenvironment, providing a more holistic view of cellular function. Recent advances in innovative spatial biology techniques now allow intact tissue sections to be examined using various -omics lenses, such as genomics, transcriptomics, proteomics, and metabolomics, with spatial data. This fusion of approaches provides researchers with critical insights into the molecular composition and functions of the cells and tissues at precise spatial coordinates. Furthermore, advanced imaging techniques, including high-resolution microscopy, hyperspectral imaging, and mass spectrometry imaging, enable the visualization and analysis of the spatial distribution of biomolecules, cells, and tissues. Linking these molecular imaging outputs to conventional tissue histology can facilitate a more comprehensive characterization of disease phenotypes. This review summarizes the recent advancements in the molecular imaging modalities and methodologies for in-depth spatial analysis. It explores their applications, challenges, and potential opportunities in the field of OA. Additionally, this review provides a perspective on the potential research directions for these contemporary approaches that can meet the requirements of clinical diagnoses and the establishment of therapeutic targets for OA. [ABSTRACT FROM AUTHOR]

The anatomy of the osteochondral junction is complex because several tissue components exist as a unit, including uncalcified cartilage (with superficial, middle, and deep layers), calcified cartilage, and subchondral bone. Furthermore, it is difficult to study because this region is made up of a variety of cell types and extracellular matrix compositions. Using X-ray fluorescence microscopy, we present a protocol for simultaneous elemental detection on fresh frozen samples. We transferred the osteochondral sample using a tape-assisted system and successfully tested it in synchrotron X-ray fluorescence. This protocol elucidates the distinct distribution of elements at the human knee's osteochondral junction, making it a useful tool for analyzing the co-distribution of various elements in both healthy and diseased states. [ABSTRACT FROM AUTHOR]

Purpose of the Review: Osteoarthritis (OA) is a multifactorial and progressive disease affecting whole synovial joint. The extract pathogenic mechanisms and diagnostic biomarkers of OA remain unclear. In this article, we review the studies related to metabolomics of OA, discuss the biomarkers as a tool for early OA diagnosis. Furthermore, we examine the major studies on the application of metabolomics methodology in the complex context of OA and create a bridge from findings in basic science to their clinical utility. Recent Findings: Recently, the tissue metabolomics signature permits a view into transitional phases between the healthy and OA joint. Both nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry-based metabolomics approaches have been used to interrogate the metabolic alterations that may indicate the complex progression of OA. Specifically, studies on alterations pertaining to lipids, glucose, and amino acid metabolism have aided in the understanding of the complex pathogenesis of OA. Summary: The discovery of identified metabolites could be important for diagnosis and staging of OA, as well as for the assessment of efficacy of new drugs. [ABSTRACT FROM AUTHOR]