The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous forAdamts4orAdamts5null alleles after spinal cord injury (SCI). ADAMTS-derived 50–60 kDa aggrecan and 50 kDa brevican fragments were observed inAdamts4−/−,Adamts5−/−, andwtmice but not in the sham-operated group. By contrastAdamts4−/−andAdamts5−/−mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot inAdamts4−/−mice’ spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated inAdamts4−/−orAdamts5−/−mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI.

Playing a key role in the pathophysiology of many diseases, A Disintegrin-like and Metalloproteinase with Thrombospondin type-1 motif (ADAMTS) proteinases have been attracted more attention in obstetrics and gynecology. First discovered in 1997, this zinc-dependent proteinase family has 19 members today. These enzymes, which are located in the extracellular matrix (ECM), have a lot of very important functions, like matrix formation and resorption, angiogenesis, ovulation, and coagulation. In addition, in the pathogenesis of cancer, inflammation, arthritis, and connective tissue diseases, ADAMTS proteinases have crucial roles. The purpose of this review is to collect previous studies about obstetrics and gynecology that are related to ADAMTS enzymes and discuss the subject in many aspects to give an idea to the investigators who are interested in the subject.

Nuclear factor-κB (NF-κB) is involved in the regulation of inflammation‑associated genes. NF-κB forms dimers which bind with sequences referred to as NF-κB sites (9-11 bp). A disintegrin-like and metalloproteinase with thrombospondin type 1 motif 9 (ADAMTS9) is a type of proteoglycanase, which proteolytically cleaves versican and aggrecan. ADAMTS9 is a cytokine-inducible gene that contains binding sites for NF-κB within its promoter region. Interleukin-1β (IL-1β) affects cartilage metabolism and is involved in the NF-κB pathway. It is therefore hypothesized that NF-κB binding with ADAMTS9 promoters may activate IL-1β, thereby promoting chondrocytic cell growth. In the present study, the OUMS-27 chondrocytic human chondrosarcoma cell line was treated with IL-1β with or without inhibitors of NF-κB signaling pathways. Chromatin immunoprecipitation (ChIP) and electromobility shift assays (EMSA) were conducted order to analyze the binding of NF-κB with the ADAMTS9 promoter region. NF-κB-p65 subunit phosphorylation was promoted in IL-1β-treated cells, which were not treated with inhibitors of NF-κB signaling pathways. By contrast, NF-κB-p65 subunit phosphorylation was inhibited in cells that had been treated with BAY-117085, an NF-κB pathway inhibitor. ChIP and EMSA assays demonstrated that, following treatment with IL-1β, NF-κB‑p65 bound to elements located at -1177 and -1335 in the ADAMTS9 promoter region, in contrast to the untreated samples. The results of the present study suggested that NF-κB may be involved in IL-1β-induced activation of ADAMTS9 in human chondrocytes.