Device-Based Enrichment of Knee Joint Synovial Cells to Drive MSC Chondrogenesis Without Prior Culture Expansion In Vitro: A Step Closer to 1-Stage Orthopaedic Procedures.

Background: Synovial fluid (SF) mesenchymal stem cells (MSCs) are derived from the synovial membrane and have cartilage repair potential. Their current use in clinical practice is largely exploratory. As their numbers tend to be small, therapeutic procedures using MSCs typically require culture expansion.

Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint Distraction.

Osteoarthritis (OA) is the most common musculoskeletal disorder. Although joint replacement remains the standard of care for knee OA patients, knee joint distraction (KJD), which works by temporarily off-loading the joint for 6-8 weeks, is becoming a novel joint-sparing alternative for younger OA sufferers. The biological mechanisms behind KJD structural improvements remain poorly understood but likely involve joint-resident regenerative cells including multipotent stromal cells (MSCs).

The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone.

Osteoarthritis (OA), the most common joint disorder, is characterised by progressive structural changes in both the cartilage and the underlying subchondral bone. In late disease stages, subchondral bone sclerosis has been linked to heightened osteogenic commitment of bone marrow stromal cells (BMSCs). This study utilised cell sorting and immunohistochemistry to identify a phenotypically-distinct, osteogenically-committed BMSC subset in human OA trabecular bone.

Actin Mutations and Their Role in Disease.

Actin is a widely expressed protein found in almost all eukaryotic cells. In humans, there are six different genes, which encode specific actin isoforms. Disease-causing mutations have been described for each of these, most of which are missense.

The novel cytokine Metrnl/IL-41 is elevated in Psoriatic Arthritis synovium and inducible from both entheseal and synovial fibroblasts.

Meteorin-like(IL-41), is a novel cytokine that is thought to be immunoregulatory and is highly expressed in psoriatic skin. We investigated IL-41 protein expression in synovial tissue in RA(Rheumatoid Arthritis), PsA(Psoriatic Arthritis) and OA(Osteoarthritis) patients and evaluated IL-41 production from healthy enthesis samples, as the enthesis represent the primary inflammatory site in PsA. IL-41 was measured in synovial fluid from PsA, RA and OA patients.

Gene expression and functional comparison between multipotential stromal cells from lateral and medial condyles of knee osteoarthritis patients.

Osteoarthritis (OA) is the most common degenerative joint disorder. Multipotential stromal cells (MSCs) have a crucial role in joint repair, but how OA severity affects their characteristics remains unknown. Knee OA provides a good model to study this, as osteochondral damage is commonly more severe in the medial weight-bearing compartment compared to lateral side of the joint.

The simultaneous analysis of mesenchymal stem cells and early osteocytes accumulation in osteoarthritic femoral head sclerotic bone.

Objective: OA subchondral bone is a key target for therapy development. Osteocytes, the most abundant bone cell, critically regulate bone formation and resorption. Their progenitors, mesenchymal stem cells (MSCs), display altered behaviour in osteoarthritic subchondral bone.

A Novel Arthroscopic Technique for Intraoperative Mobilization of Synovial Mesenchymal Stem Cells.

Background: Mesenchymal stem cells (MSCs) have emerged as a promising candidate for tissue regeneration and restoration of intra-articular structures such as cartilage, ligaments, and menisci. However, the routine use of MSCs is limited in part by their low numbers and the need for methods and procedures outside of the joint or surgical field.

Purpose: To demonstrate feasibility of a technique in which minimally manipulated synovial MSCs can be mobilized during knee arthroscopy, thereby showing proof of concept for the future evaluation and clinical use of native joint resident MSCs in single-stage joint repair strategies.

Is Knee Joint Distraction a Viable Treatment Option for Knee OA?-A Literature Review and Meta-Analysis.

Knee joint distraction (KJD) is a new application of an established technique to regenerate native cartilage using an external fixator. The purpose of this study is to perform a systematic review and meta-analysis of the literature to determine whether KJD is beneficial for knee osteoarthritis and how results compare with established treatments. Studies assessing the outcomes of KJD were retrieved, with three studies (one cohort and two randomized controlled trials), 62 knees, meeting the inclusion criteria.

Platelet lysate enhances synovial fluid multipotential stromal cells functions: Implications for therapeutic use.

Background Aims: Although intra-articular injection of platelet products is increasingly used for joint regenerative approaches, there are few data on their biological effects on joint-resident multipotential stromal cells (MSCs), which are directly exposed to the effects of these therapeutic strategies. Therefore, this study investigated the effect of platelet lysate (PL) on synovial fluid-derived MSCs (SF-MSCs), which in vivo have direct access to sites of cartilage injury.

Methods: SF-MSCs were obtained during knee arthroscopic procedures (N = 7).

Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis.

The role of native (not culture-expanded) joint-resident mesenchymal stem cells (MSCs) in the repair of joint damage in osteoarthritis (OA) is poorly understood. MSCs differ from bone marrow-residing haematopoietic stem cells in that they are present in multiple niches in the joint, including subchondral bone, cartilage, synovial fluid, synovium and adipose tissue. Research in experimental models suggests that the migration of MSCs adjacent to the joint cavity is crucial for chonodrogenesis during embryogenesis, and also shows that synovium-derived MSCs might be the primary drivers of cartilage repair in adulthood.

Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies.

Objectives.: The SpAs are genetically and therapeutically linked to IL-23, which in turn regulates IL-22, a cytokine that has been implicated in the regulation of new bone formation in experimental models. We hypothesize that IL-22, a master regulator of stem cells in other niches, might also regulate human mesenchymal stem cell (MSC) osteogenesis.

A Combination of Diffusion and Active Translocation Localizes Myosin 10 to the Filopodial Tip.

Myosin 10 is an actin-based molecular motor that localizes to the tips of filopodia in mammalian cells. To understand how it is targeted to this distinct region of the cell, we have used total internal reflection fluorescence microscopy to study the movement of individual full-length and truncated GFP-tagged molecules. Truncation mutants lacking the motor region failed to localize to filopodial tips but still bound transiently at the plasma membrane.

A nuclear magnetic resonance study of water in aggrecan solutions.

Aggrecan, a highly charged macromolecule found in articular cartilage, was investigated in aqueous salt solutions with proton nuclear magnetic resonance. The longitudinal and transverse relaxation rates were determined at two different field strengths, 9.4 T and 0.

Synovial fluid hyaluronan mediates MSC attachment to cartilage, a potential novel mechanism contributing to cartilage repair in osteoarthritis using knee joint distraction.

Objectives: Knee joint distraction (KJD) is a novel, but poorly understood, treatment for osteoarthritis (OA) associated with remarkable 'spontaneous' cartilage repair in which resident synovial fluid (SF) multipotential mesenchymal stromal cells (MSCs) may play a role. We hypothesised that SF hyaluronic acid (HA) inhibited the initial interaction between MSCs and cartilage, a key first step to integration, and postulate that KJD environment favoured MSC/cartilage interactions.

Methods: Attachment of dual-labelled SF-MSCs were assessed in a novel in vitro human cartilage model using OA and rheumatoid arthritic (RA) SF.

Intrinsic multipotential mesenchymal stromal cell activity in gelatinous Heberden's nodes in osteoarthritis at clinical presentation.

Introduction: Gelatinous Heberden's nodes (HNs), also termed synovial cysts, are a common form of generalized osteoarthritis (OA). We sought to determine whether HN cases at clinical presentation contained multipotential stromal cells (MSCs) and to explore whether such cells were more closely related to bone marrow (BM) or synovial fluid (SF) MSCs by transcriptional analysis.

Methods: At clinical presentation, gelatinous material was extracted/extruded from the distal phalangeal joint of OA patients with HNs.

Multipotential stromal cell abundance in cellular bone allograft: comparison with fresh age-matched iliac crest bone and bone marrow aspirate.

Aim: To enumerate and characterize multipotential stromal cells (MSCs) in a cellular bone allograft and compare with fresh age-matched iliac crest bone and bone marrow (BM) aspirate.

Materials & Methods: MSC characterization used functional assays, confocal/scanning electron microscopy and whole-genome microarrays. Resident MSCs were enumerated by flow cytometry following enzymatic extraction.

Native multipotential stromal cell colonization and graft expander potential of a bovine natural bone scaffold.

Graft expanders are bone scaffolds used, in combination with autografts, to fill large bone defects in trauma surgery. This study investigates the graft expander potential of a natural bone substitute Orthoss by studying its ability to support attachment, growth and osteogenic differentiation of neighboring multipotential stromal cells (MSCs). Material consisting of bone marrow (BM) aspirate and reamer-irrigator-aspirator (RIA)-harvested autograft bone was co-cultured with commercially available Orthoss granules.

The SAH domain extends the functional length of the myosin lever.

Stable, single alpha-helix (SAH) domains are widely distributed in the proteome, including in myosins, but their functions are unknown. To test whether SAH domains can act as levers, we replaced four of the six calmodulin-binding IQ motifs in the levers of mouse myosin 5a (Myo5) with the putative SAH domain of Dictyostelium myosin MyoM of similar length. The SAH domain was inserted between the IQ motifs and the coiled coil in a Myo5 HMM construct in which the levers were truncated from six to two IQ motifs (Myo5-2IQ).

A FERM domain autoregulates Drosophila myosin 7a activity.

Full-length Drosophila myosin 7a (myosin 7a-FL) has a complex tail containing a short predicted coiled coil followed by a MyTH4-FERM domain, an SH3 domain, and a C-terminal MyTH4-FERM domain. Myosin 7a-FL expressed in Sf9 cells is monomeric despite the predicted coiled coil. We showed previously that Subfragment-1 (S1) from this myosin has MgATPase of V(max) approximately 1 s(-1) and K(ATPase) approximately 1 microM actin.

Colicin N binds to the periphery of its receptor and translocator, outer membrane protein F.

Colicins kill Escherichia coli after translocation across the outer membrane. Colicin N displays an unusually simple translocation pathway, using the outer membrane protein F (OmpF) as both receptor and translocator. Studies of this binary complex may therefore reveal a significant component of the translocation pathway.