New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis

Abstract

Osteoarthritis (OA) is the most common joint disorder and affects approximately half of the aged population. Current treatments for OA are largely palliative until the articular cartilage has been deeply damaged and irreversible morphological changes appear. Thus, effective methods are needed for diagnosing and monitoring the progression of OA during its early stages when therapeutic drugs or biological agents are most likely to be effective. Various proteinases involved in articular cartilage degeneration in pre-OA conditions, which may represent the earliest reversible measurable changes, are considered diagnostic and therapeutic targets for early OA. Of these proteinases, matrix metalloproteinase 13 (MMP-13) has received the most attention, because it is a central node in the cartilage degradation network. In this review, we highlight the main MMP-13-related changes in OA chondrocytes, including alterations in the activity and expression level of MMP-13 by upstream regulatory factors, DNA methylation, various non-coding RNAs (ncRNAs), and autophagy. Because MMP-13 and its regulatory networks are suitable targets for the development of effective early treatment strategies for OA, we discuss the specific targets of MMP-13, including upstream regulatory proteins, DNA methylation, non-coding RNAs, and autophagy-related proteins of MMP-13, and their therapeutic potential to inhibit the development of OA. Moreover, the various entities mentioned in this review might be useful as early biomarkers and for personalized approaches to disease prevention and treatment by improving the phenotyping of early OA patients.

Antigen-Based Nano-Immunotherapy Controls Parasite Persistence, Inflammatory and Oxidative Stress, and Cardiac Fibrosis, the Hallmarks of Chronic Chagas Cardiomyopathy, in A Mouse Model of Trypanosoma cruzi Infection

“…MMP12 deficiency attenuated the angiotensin II-induced vascular injury, tissue infiltration of M2 macrophages, and heart fibrosis in mice [48]. MMP-13 has received attention because of its central role in the cartilage degradation network and it is also proposed to have anti-fibrotic activities in murine models of atherosclerosis [49]. Our studies provided the first clue to the potential role of infiltrating macrophages in signaling cardiac fibrosis in Chagas disease.…”

Circ_0136474 and MMP‐13 suppressed cell proliferation by competitive binding to miR‐127‐5p in osteoarthritis

“…Besides, MMP-13 was known to function as an extracellular matrix (ECM)-degrading enzyme in OA joints. 15,16 In clinical samples, MMP-13 was abnormally expressed during different stages of OA process and was found to up-regulated during the early stage and down-regulated during the late stage in human OA cartilage, which indicated its central node in the cartilage degradation network and contribution of MMP-13 to the initiation/ onset of OA. 17,18 In addition, the activity of MMP-13 can be regulated at multiple levels, including epigenetic modification, transcriptional regulation and post-transcriptional regulation by ncRNAs.…”

“…Among these MMPs, MMP‐13 has caught a lot of attention in that it was significantly overexpressed in both joints and articular cartilage in OA patients and could hardly be detected in normal tissues. Besides, MMP‐13 was known to function as an extracellular matrix (ECM)‐degrading enzyme in OA joints . In clinical samples, MMP‐13 was abnormally expressed during different stages of OA process and was found to up‐regulated during the early stage and down‐regulated during the late stage in human OA cartilage, which indicated its central node in the cartilage degradation network and contribution of MMP‐13 to the initiation/onset of OA .…”

Transcriptional response of human articular chondrocytes treated with fibronectin fragments: anin vitromodel of the osteoarthritis phenotype

“…Upregulated genes also included proteases such as MMP13 and MMP10 (both 12-fold). Matrix metallopeptidase 13 (MMP13) is an enzyme that degrades type II collagen and is thought to play a critical role in cartilage degradation in OA 12,15,[25][26][27][28] . Interestingly, among the downregulated genes were the collagen-binding integrins ITGA10 and ITGA11, which decreased 3.7-and 3.5-fold, respectively.…”