Real-world registry-based study on apremilast use in psoriasis and psoriatic arthritis in Finland.

Objectives: This study assessed the position of apremilast in the treatment pathway of psoriasis (PsO) and psoriatic arthritis (PsA) in Finnish clinical practice, compared the characteristics of apremilast and biologic therapy users, evaluated persistence with apremilast and identified factors influencing treatment discontinuation.

Method: This retrospective study used data from Finnish national health registries. The target group was identified based on L40* diagnosis and medication records between 2015 and 2018.

First-in-Humans Study of Ga-DOTA-Siglec-9, a PET Ligand Targeting Vascular Adhesion Protein 1.

Sialic acid-binding immunoglubulinlike lectin 9 (Siglec-9) is a ligand of vascular adhesion protein 1. A Ga-labeled peptide of Siglec-9, Ga-DOTA-Siglec-9, holds promise as a novel PET tracer for imaging of inflammation. This first-in-humans study investigated the safety, tolerability, biodistribution, and radiation dosimetry of this radiopharmaceutical.

Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation.

Cathepsin K (CTSK) is secreted by osteoclasts to degrade collagen and other matrix proteins during bone resorption. Global deletion of Ctsk in mice decreases bone resorption, leading to osteopetrosis, but also increases the bone formation rate (BFR). To understand how Ctsk deletion increases the BFR, we generated osteoclast- and osteoblast-targeted Ctsk knockout mice using floxed Ctsk alleles.

Mice with tissue inhibitor of metalloproteinases 4 (Timp4) deletion succumb to induced myocardial infarction but not to cardiac pressure overload.

Tissue inhibitor of metalloproteinases 4 (TIMP4) is expressed highly in heart and found dysregulated in human cardiovascular diseases. It controls extracellular matrix remodeling by inhibiting matrix metalloproteinases (MMPs) and is implicated in processes including cell proliferation, apoptosis, and angiogenesis. Timp4-deficient mice (Timp4(-/-)) were generated to assess TIMP4 function in normal development and in models of heart disease.

Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology.

Tissue inhibitors of matrix metalloproteinases (TIMPs) comprise a family of four members, of which TIMP4 is characterized by being primarily restricted to cardiovascular structures. We demonstrate with immunohistochemical analysis of healthy human tissue that TIMP4 is present in medial smooth muscle cells and adventitial capillaries of arteries as well as in cardiomyocytes. Animal studies have suggested a role for TIMP4 in several inflammatory diseases and cardiovascular pathologies.

Individual Timp deficiencies differentially impact pro-MMP-2 activation.

Membrane-type matrix metalloproteinases (MT-MMPs) have emerged as key enzymes in tumor cell biology. The importance of MT1-MMP, in particular, is highlighted by its ability to activate pro-MMP-2 at the cell surface through the formation of a trimolecular complex comprised of MT1-MMP/tissue inhibitor of metalloproteinase-2 (TIMP-2)/pro-MMP-2. TIMPs 1-4 are physiological MMP inhibitors with distinct roles in the regulation of pro-MMP-2 processing.

Mice with a deletion in the first intron of the Col1a1 gene develop age-dependent aortic dissection and rupture.

The functional significance of the first intron of the Col1a1 gene in regulation of type I collagen synthesis remains uncertain. A previous study in mice established that a mutated Col1a1 allele that lacked a large fraction of the first intron, but retained the sequences required for normal splicing, was subject to an age- and tissue-dependent decrease in expression. In this study, we report that mice homozygous for this deletion are predisposed to dissection and rupture of the aorta during their adult life.

Characterization of the murine Timp4 gene, localization within intron 5 of the synapsin 2 gene and tissue distribution of the mRNA.

Tissue inhibitor of matrix metalloproteinases type 4 (TIMP-4), the newest member in the mammalian TIMP family of inhibitors of matrix metalloproteinases (MMPs), differs from the other three TIMPs by its restricted expression pattern. This suggests that TIMP-4 could play a role in tissue-specific regulation of extracellular matrix (ECM) turnover. To define this role, modulation of TIMP-4 production by overexpression, aberrant expression and inactivation of the Timp4 gene in transgenic mice should be performed.