Histone Extraction From Human Articular Cartilage for the Study of Epigenetic Regulation in Osteoarthritis

[Abstract] Osteoarthritis (OA) is a chronic disease that affects articular cartilage, causing its degeneration. Although OA is one of the most prevalent pathologies globally, there are no definitive treatments available. Recently, research has focused on elucidating the complex interplay that takes place between inflammatory processes and epigenetic regulation, showing that histone post-translational modifications (PTMs) can exert a pronounced effect on the expression of OA-related genes. OA chondrocytes enhance the production of interleukin 1β (IL-1β) and interleukin 8 (IL-8), which are epigenetically regulated. These cytokines upregulate the synthesis of matrix metalloproteinases (MMPs) and aggrecanases, which promote the extracellular matrix (ECM) destruction. This motivates the study of histone PTMs to investigate the epigenetic regulation of proinflammatory molecules, but the absence of specific protocols to extract histones from human articular cartilage has complicated this task. The lack of effective methods can be explained by the structural complexity and low cellularity of this tissue, which are responsible for the biomechanical properties that allow the movement of the joint but also complicate histone isolation. Here, we provide a histone extraction procedure specifically adapted for cryopreserved human articular cartilage that can be useful to understand epigenetic regulation in OA and accelerate the search for novel strategies.This research was funded by Instituto de Salud Carlos III (grant No. PI19/01213 and grant No. RD21/0002/0009), integrated in the National Plan for Scientific Research, Development and Technological Innovation 2017–2020 and funded by the ISCIII —General Subdirection of Assessment and Promotion of the Research—European Regional Development Fund (FEDER) “A way of making Europe”. M.C.D.A is supported by the Miguel Servet program from Fondo Investigación Sanitaria-Spain (CP18/00084). Also, by Xunta de Galicia (grant No. IN607A 2021/7). The Biomedical Research Networking Center (CIBER) is an initiative from Instituto de Salud Carlos III (ISCIII)Xunta de Galicia; IN607A 2021/