A5067517660- Osteoarthritis Treatment and Mechanisms
- Autophagy in Disease and Therapy
- Adenosine and Purinergic Signaling
- Connective tissue disorders research
- Sirtuins and Resveratrol in Medicine
- Bone Metabolism and Diseases
- RNA Research and Splicing
- Developmental Biology and Gene Regulation
- Molecular Biology Techniques and Applications
- Proteoglycans and glycosaminoglycans research
- Chemokine receptors and signaling
- Cellular Mechanics and Interactions
- Hedgehog Signaling Pathway Studies
- Autoimmune and Inflammatory Disorders Research
- Cancer Cells and Metastasis
- Pluripotent Stem Cells Research
- Immune cells in cancer
- Fibroblast Growth Factor Research
- Mesenchymal stem cell research
- Multiple Myeloma Research and Treatments
- Cancer-related molecular mechanisms research
- Phagocytosis and Immune Regulation
- Single-cell and spatial transcriptomics
- Anesthesia and Neurotoxicity Research
- Cannabis and Cannabinoid Research
Karolinska Institutet
2016-2025
Queen Astrid Military Hospital
2025
Sachs' Children and Youth Hospital
2024
Karolinska University Hospital
2014-2023
Stockholm University
2018
University of Edinburgh
2010-2015
University of Manchester
2010
Roslin Institute
2010
Objectives It has been suggested that the lysosomal recycling process called macro-autophagy plays a role in osteoarthritis development. We thus decided to genetically ablate autophagy-indispensable Atg5 gene specifically chondrocytes and analyse development of upon aging post-traumatic model. Methods Mice lacking their (Atg5cKO) were generated by crossing Atg5-floxed mice with transgenic expressed cre recombinase driven collagen type 2 promoter. Animals analysed at age 2, 6 12 months for...
Articular cartilage has little regenerative capacity. Recently, genetic lineage tracing experiments have revealed chondrocyte progenitors at the articular surface. We further characterized these by using in vivo approaches. Histone H2B-green fluorescent protein retention that superficial cells divide more slowly than underlying chondrocytes. Clonal combined with immunohistochemistry renew their number symmetric division, express mesenchymal stem cell markers, and generate chondrocytes via...
BackgroundResolution of inflammation is an active and dynamic process after surgery. Maresin 1 (MaR1) one a growing number specialised pro-resolving lipids biosynthesised by macrophages that regulates acute inflammation. We investigated the effects MaR1 on postoperative neuroinflammation, macrophage activity, cognitive function in mice.MethodsAdult male C57BL/6 (n=111) Ccr2RFP/+Cx3cr1GFP/+ (n=54) mice were treated with before undergoing anaesthesia orthopaedic Systemic inflammatory changes,...
Abstract Spatially resolved transcriptomics has enabled precise genome-wide mRNA expression profiling within tissue sections. The performance of methods targeting the polyA tails relies on availability specimens with high RNA quality. Moreover, cost currently available spatial assays requires a careful sample screening process to increase chance obtaining high-quality data. Indeed, upfront analysis quality can show considerable variability due handling, storage, and/or intrinsic factors. We...
The development of chondrogenic cell lines has led to major advances in the understanding how chondrocyte differentiation is regulated, and uncovered many signalling pathways gene regulatory mechanisms required maintain normal function. ATDC5 cells are a well established vitro model endochondral ossification; however, current methods limited for mineralisation studies. In this study we demonstrate that culturing presence ascorbic acid 10 mM β-glycerophosphate (βGP) significantly increases...
Surgery and critical illness often associate with cognitive decline. Surgical trauma or infection can lead independently to learning memory impairments via similar, but not identical, cellular signaling of the innate immune system that promotes neuroinflammation. In this study we explored putative synergism between aseptic orthopedic surgery infection, latter reproduced by postoperative lipopolysaccharide (LPS) administration. We observed LPS augmented systemic inflammation up d 3 was...
ABSTRACT Longitudinal bone growth takes place in epiphyseal plates located the ends of long bones. The plate consists chondrocytes traversing from undifferentiated (resting zone) to terminally differentiated (hypertrophic stage. Autophagy is an intracellular catabolic process lysosome-dependent recycling organelles and protein complexes. activated during nutritionally depleted or hypoxic conditions order facilitate cell survival. Chondrocytes middle are owing avascular nature plate....
The gene IL6ST encodes GP130, the common signal transducer of IL-6 cytokine family consisting 10 cytokines. Previous studies have identified cytokine-selective defects that preserve LIF signaling. We describe three unrelated families with at least five affected individuals who presented lethal Stüve-Wiedemann–like syndrome characterized by skeletal dysplasia and neonatal lung dysfunction additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities,...
Cartilaginous structures are at the core of embryo growth and shaping before bone forms. Here we report a novel principle vertebrate cartilage that is based on introducing transversally-oriented clones into pre-existing cartilage. This mechanism uncouples lateral expansion curved cartilaginous sheets from control thickness, process which might be evolutionary underlying adaptations facial shape. In rod-shaped (Meckel, ribs skeletal elements in developing limbs), transverse integration clonal...
Growth plate and articular cartilage constitute a single anatomical entity early in development but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears animals conquering land - amniotes. Analysis of pattern mammals with specialized extremities (whales, bats, jerboa) revealed correlates extent mechanical loads. Mathematical modeling reduces stress within growth plate....
Emerging evidence indicates that dietary nitrate can reverse several features of the metabolic syndrome, but underlying molecular mechanisms still remain elusive. The aim present study was to explore involved in effects on dysfunctions induced by high-fat diet (HFD) mice. Four weeks old C57BL/6 male mice, exposed HFD for ten weeks, were characterised increased body weight, fat content, fasting glucose and impaired clearance. All these abnormalities significantly attenuated nitrate....
Mechanistic target of rapamycin (serine/threonine kinase) complex 1 (MTORC1) is a protein-signaling at the fulcrum anabolic and catabolic processes, which acts depending on wide-ranging environmental cues. It generally accepted that lysosomes facilitate MTORC1 activation by generating an internal pool amino acids. Amino acids activate stimulating its translocation to lysosomal membrane where it forms super-complex involving lysosomal-membrane-bound vacuolar-type H(+)-ATPase (v-ATPase) proton...
Incomplete mapping of gene expression within human (epiphyseal) growth plates contributes to the challenges diagnosing and treating patients with skeletal disorders. To address this issue, we applied spatially resolved transcriptomics rare plate biopsies obtained from healthy adolescents. In addition identifying novel markers each zone plate, spatial profiling revealed that genes associated poorly understood disorders, including NKX3-2, SGMS2 WNK4, is restricted specific zones. By...
The skeletal ciliopathies are a heterogeneous group of disorders with significant clinical and genetic variability the main features thoracic hypoplasia short tubular bones. To date, 25 genes have been identified in association ciliopathies. Mutations KIAA0753 gene recently associated Joubert syndrome (JBTS) orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants four patients short-rib type dysplasia. manifestations our variable ranging from fetal lethal to viable moderate...
Abstract There are major differences in duration and scale at which limb development regeneration proceed, raising the question to what extent is a recapitulation of development. We address this by analyzing skeletal elements using combination micro-CT imaging, molecular profiling clonal cell tracing. find that, contrast development, regenerative growth accomplished based entirely on cartilage expansion prior ossification, not limiting transversal resulting bulkier parts. The oriented...
ABSTRACT The bone marrow (BM) is a complex tissue where spatial relationships influence cell behavior, signaling, and function. Consequently, understanding the whole dynamics of cellular interactions requires complementary techniques that preserve map architecture populations in situ . We successfully conducted transcriptional profiling using Visium Spatial Gene Expression formalin-fixed paraffin-embedded (FFPE) BM samples obtained from healthy Multiple Myeloma (MM) mouse models patients,...
Tartrate-resistant acid phosphatase (TRAP) serum levels reflect osteoclast number, bone remodeling activity, and fracture risk. Deletion or loss of function TRAP results in short stature mice man. Yet, the impact mechanisms for site- sex-specific development cartilage is not well understood. Here, we use a global knockout (TRAPKO) wildtype littermate control (WT) both sexes to investigate as possible sex- site-specific regulator growth plate development. TRAPKO weighed less had shorter...
There are several pitfalls associated with research based on transgenic mice. Here, we describe our interpretation and analysis of mTORC1 activation in growth plate chondrocytes compare these to a recent publication (Yan et al., Nature Communications 2016, 7:11151). Both laboratories employed TSC1-floxed mice crossed collagen type 2-driven Cre (Col2-Cre), but drew substantially different conclusions. It was reported that mechanistic target rapamycin complex 1 (mTORC1) via Tsc1 ablation...
The development of craniofacial skeletal structures is fascinatingly complex and elucidation the underlying mechanisms will not only provide novel scientific insights, but also help develop more effective clinical approaches to treatment and/or prevention numerous congenital malformations. To this end, we performed a genome-wide analysis RNA transcription from non-coding regulatory elements by CAGE-sequencing facial mesenchyme human embryos cross-checked active enhancers thus identified...
Abstract Growth plate and articular cartilage constitute a single anatomical entity early in development, but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears animals conquering land - amniotes. Analysis of pattern mammals with specialized extremities (whales, bats, jerboa) revealed development correlates extent mechanical loads. Mathematical modelling reduces...