A5049894537- Bone Metabolism and Diseases
- Bone health and treatments
- Connective tissue disorders research
- Wnt/β-catenin signaling in development and cancer
- Bone and Dental Protein Studies
- Cancer-related gene regulation
- Bone health and osteoporosis research
- Adipose Tissue and Metabolism
- Bone and Joint Diseases
- Nutrition and Health in Aging
- NF-κB Signaling Pathways
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- TGF-β signaling in diseases
- Neonatal Respiratory Health Research
- GDF15 and Related Biomarkers
- Muscle Physiology and Disorders
- Protease and Inhibitor Mechanisms
- Histone Deacetylase Inhibitors Research
- Parathyroid Disorders and Treatments
- Molecular Biology Techniques and Applications
- Dermatological and Skeletal Disorders
- Dental Implant Techniques and Outcomes
- Lower Extremity Biomechanics and Pathologies
- Peptidase Inhibition and Analysis
University of Turku
2013-2024
Turku University Hospital
2013-2024
Harvard University
2008-2022
University of Helsinki
2015
Turku PET Centre
2012-2014
Harvard University Press
2013
Institute of Infection and Immunity
2013
Massachusetts General Hospital
2012-2013
Hadassah Medical Center
2013
Boston University
2010
This report identifies human skeletal diseases associated with mutations in WNT1. In 10 family members dominantly inherited, early-onset osteoporosis, we identified a heterozygous missense mutation WNT1, c.652T→G (p.Cys218Gly). separate 2 siblings affected by recessive osteogenesis imperfecta, homozygous nonsense mutation, c.884C→A, p.Ser295*. vitro, aberrant forms of the WNT1 protein showed impaired capacity to induce canonical WNT signaling, their target genes, and mineralization. mice,...
Cathepsin K (CTSK) is secreted by osteoclasts to degrade collagen and other matrix proteins during bone resorption. Global deletion of Ctsk in mice decreases resorption, leading osteopetrosis, but also increases the formation rate (BFR). To understand how BFR, we generated osteoclast- osteoblast-targeted knockout using floxed alleles. Targeted ablation hematopoietic cells, or specifically cells monocyte-osteoclast lineage, resulted increased volume BFR as well osteoclast osteoblast numbers....
Cortical-bone fragility is a common feature in osteoporosis that linked to nonvertebral fractures. Regulation of cortical-bone homeostasis has proved elusive. The study genetic disorders the skeleton can yield insights fuel experimental therapeutic approaches treatment rare and skeletal ailments.We evaluated four patients with Pyle's disease, disorder characterized by thinning, limb deformity, fractures; two were examined means exome sequencing, Sanger sequencing. After candidate gene was...
While there has been significant progress in determining the transcriptional cascade involved terminal adipocyte differentiation, less is known about early events leading to lineage commitment and cell fate choice. It recently discovered that zinc finger protein 423 (Zfp423) an actor adipose determination. Here, we show a close paralog of Zfp423, Zfp521, acts as key regulator differentiation vitro vivo. Zfp521 exerts its actions by binding B factor 1 (Ebf1), transcription required for...
Abstract This study is based on a hypothesis that overexpression of an osteoclast enzyme, cathepsin K, causes imbalance in bone remodeling toward loss. The was tested transgenic (TG) mice harboring additional copies the murine K gene (Ctsk) identifiable by silent mutation engineered into construct. For this study, three TG mouse lines 3-25 transgene were selected. Tissue specificity expression determined Northern analysis, which revealed up to 6-fold increases levels messenger RNA (mRNA)...
Runx2 is indispensable for osteoblast lineage commitment and early differentiation but also blocks maturation, thereby causing bone loss in transgenic mice. Zinc finger protein 521 (Zfp521) antagonizes vivo. Eliminating one Zfp521 allele mitigates the cleidocranial dysplasia–like phenotype of newborn Runx2+/− mice, whereas overexpressing exacerbates it. Overexpressing reverses severe osteopenia adult binds to both histone deacetylase 3 (HDAC3), promotes their association, transcriptional...
Tissue inhibitor of metalloproteinases 4 (TIMP4) is expressed highly in heart and found dysregulated human cardiovascular diseases. It controls extracellular matrix remodeling by inhibiting (MMPs) implicated processes including cell proliferation, apoptosis, angiogenesis. Timp4-deficient mice (Timp4−/−) were generated to assess TIMP4 function normal development models disease. We deleted exons 1–3 the Timp4 gene homologous recombination. Timp4−/− are born healthy, develop normally, produce...
Lactation induces bone loss to provide sufficient calcium in the milk, a process that involves osteoclastic resorption but also osteocytes and perilacunar resorption. The exact mechanisms by which contribute remain elusive. Osteocytes express genes required osteoclasts for resorption, including cathepsin K (Ctsk), lactation elevates their expression. We show Ctsk deletion prevented increase osteocyte lacunar area seen during lactation, as well effects of osteoclast numbers decrease...
Abstract Context Bone marrow (BM) in adult long bones is rich adipose tissue, but the functions of BM adipocytes are largely unknown. We set out to elucidate metabolic and molecular characteristics tissue (BMAT) humans. Objective Our aim was determine if BMAT an insulin-sensitive whether insulin sensitivity altered obesity or type 2 diabetes (T2DM). Design This a cross-sectional longitudinal study. Setting The study conducted clinical research center. Patients Other Participants glucose...
Non-pharmacological interventions are important in reducing risk for osteoporotic fractures. We investigated the effects of a 16-week individualized resistance training intervention on bone mineral density (BMD), turnover markers and 10-year relative (RR) fracture.Interventional study with follow-up.In total, 37 elderly women (mean age 71.9 ± 3.1 years) decreased muscle strength participated three times per week 60 min session 16 weeks under supervision licensed physiotherapist. Total hip...
ABSTRACT Human genetic evidence demonstrates that WNT1 mutations cause osteogenesis imperfecta (OI) and early-onset osteoporosis, implicating as a major regulator of bone metabolism. However, its main cellular source mechanisms action in remain elusive. We generated global limb bud mesenchymal cell–targeted deletion Wnt1 mice. Heterozygous resulted mild trabecular osteopenia due to decreased osteoblast function. Targeted progenitors led spontaneous fractures impaired function increased...
Abstract Objective Several recent studies have demonstrated that cathepsin K, a proteolytic enzyme capable of degrading native fibrillar collagen, is overexpressed in osteoarthritic cartilage and inflamed synovial tissue. However, it not known whether increased K production primary or secondary event these diseases. The availability transgenic UTU17 mice, which exhibit constitutive overexpression the gene, prompted us to study possible arthritic changes their knee joints. Methods Progression...
Abstract Objective Leukocyte traffic from the blood to joints is crucial in pathogenesis of arthritis. A bifunctional endothelial cell–surface glycoprotein, AOC3 (amine oxidase, copper‐containing 3; also known as vascular adhesion protein 1), has both adhesive and enzymatic properties. We undertook this study determine contribution its oxidase activity leukocyte trafficking into inflamed vivo. Methods used gene‐modified animals, molecular modeling, an enzyme inhibitor, assays, arthritis...
Abstract Background Lung fibrosis is a devastating pulmonary disorder characterized by alveolar epithelial injury, extracellular matrix deposition and scar tissue formation. Due to its potent collagenolytic activity, cathepsin K, lysosomal cysteine protease an interesting target molecule with therapeutic potential attenuate bleomycin-induced in mice. We here tested the hypothesis that over-expression of K lungs mice protective fibrosis. Methods Wild-type overexpressing (cathepsin transgenic;...
Bone homeostasis is maintained by the coupled actions of hematopoietic bone-resorbing osteoclasts (OCs) and mesenchymal bone-forming osteoblasts (OBs). Here we identify early B cell factor 1 (Ebf1) transcriptional coregulator Zfp521 as components machinery that regulates bone through coordinated effects in both lineages. Deletion OBs led to impaired formation increased OB-dependent osteoclastogenesis (OC-genesis), deletion cells revealed a strong cell-autonomous role for OC progenitors. In...
Epigenetic mechanisms regulate osteogenic lineage differentiation of mesenchymal stromal cells. Histone methylation is controlled by multiple lysine demethylases and an important step in controlling local chromatin structure gene expression. Here, we show that the lysine-specific histone demethylase Kdm1A/Lsd1 abundantly expressed osteoblasts its suppression impairs osteoblast bone nodule formation vitro. Although Lsd1 knockdown did not affect global H3K4 levels, genome-wide ChIP-Seq...
Abstract Sperm flagellar protein 2 (SPEF2) is essential for motile cilia, and lack of SPEF2 function causes male infertility primary ciliary dyskinesia. Cilia are pointing out from the cell surface involved in signal transduction extracellular matrix, fluid flow motility. It has been shown that cilia cilia-related genes play role commitment differentiation chondrocytes osteoblasts during bone formation. Here we show expressed cartilage. The analysis a Spef2 knockout (KO) mouse model revealed...
Activation of Wnt signaling leads to high bone density. The R-spondin family four secreted glycoproteins (Rspo1-4) amplifies signaling. In humans, RSPO3 variants are strongly associated with Here, we investigated the role Rspo3 in skeletal homeostasis mice. Using a comprehensive set mouse genetic and mechanistic studies, show that appendicular skeleton, haplo-insufficiency targeted deletion Runx2 + osteoprogenitors lead an increase trabecular mass, increased number osteoblasts formation....