The Mechanism and Role of ADAMTS Protein Family in Osteoarthritis

Abstract

Osteoarthritis (OA) is a principal cause of aches and disability worldwide. It is characterized by the inflammation of the bone leading to degeneration and loss of cartilage function. Factors, including diet, age, and obesity, impact and/or lead to osteoarthritis. In the past few years, OA has received considerable scholarly attention owing to its increasing prevalence, resulting in a cumbersome burden. At present, most of the interventions only relieve short-term symptoms, and some treatments and drugs can aggravate the disease in the long run. There is a pressing need to address the safety problems due to osteoarthritis. A disintegrin-like and metalloprotease domain with thrombospondin type 1 repeats (ADAMTS) metalloproteinase is a kind of secretory zinc endopeptidase, comprising 19 kinds of zinc endopeptidases. ADAMTS has been implicated in several human diseases, including OA. For example, aggrecanases, ADAMTS-4 and ADAMTS-5, participate in the cleavage of aggrecan in the extracellular matrix (ECM); ADAMTS-7 and ADAMTS-12 participate in the fission of Cartilage Oligomeric Matrix Protein (COMP) into COMP lyase, and ADAMTS-2, ADAMTS-3, and ADAMTS-14 promote the formation of collagen fibers. In this article, we principally review the role of ADAMTS metalloproteinases in osteoarthritis. From three different dimensions, we explain how ADAMTS participates in all the following aspects of osteoarthritis: ECM, cartilage degeneration, and synovial inflammation. Thus, ADAMTS may be a potential therapeutic target in osteoarthritis, and this article may render a theoretical basis for the study of new therapeutic methods for osteoarthritis.

General Control Non-derepressible 2 Alleviates Cartilage Degeneration and Inhibits NLRP3 Inflammasome Activation in Osteoarthritis

“…23 ADAMTS-5 (aggrecanase-2) is a vital member of the ADAMTS metalloproteinase family, which participates in cartilage degradation. 24 In our study, GCN2 was lowly expressed in OA. Moreover, we also demonstrated that the upregulation of GCN2 significantly ameliorated ACLT-induced degeneration of articular cartilage and inflammation in rats.…”

Bulk RNA‐seq analyses of mandibular condylar cartilage in a post‐traumatic TMJ osteoarthritis rabbit model

“…DE analysis revealed 1005 DEGs between the SZ and injured SZ tissues with 472 genes were upregulated and 533 genes were downregulated in the injured SZ group (Figure 4A). Protease enzymes that mediate cartilage destruction during OA were significantly upregulated in the injured SZ tissues, including ADAMTS3 , ADAMTS5 and ADAMTS16 , that represent members of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family 27 (Figure 4B). Markers for mesenchymal skeletal stem/progenitor cells ( PTCH1 , GLI1 , PRRX1 ) were downregulated in injured SZ tissues, suggesting that stem/progenitor cell pool is depleted upon TMJ injury (Figure 4C).…”

Serum ADAMTS-9 Level in Newborn Babies with Congenital Heart Disease

“…Many studies have been done on the ADAMTS enzyme family, and their relationship with diseases such as genetic diseases, chronic diseases, and cancer has been evaluated in these studies (7)(8)(9)(10)(11)(12)(13). It has also been reported that some subtypes of this enzyme family may be associated with inflammatory diseases such as osteoarthritis (29)…”