Periostin expression in neoplastic and non-neoplastic diseases of bone and joint.

Background: Periostin is a matricellular protein that is expressed in bone and joint tissues. To determine the expression of periostin in primary bone tumours and to assess whether it plays a role in tumour progression, we carried out immunohistochemistry and ELISA for periostin in a range of neoplastic and non-neoplastic bone and joint lesions.

Methods: 140 formalin-fixed paraffin-embedded sections of bone tumours and tumour-like lesions were stained by an indirect immunoperoxidase technique with a polyclonal anti-periostin antibody.

Translocator Protein as an Imaging Marker of Macrophage and Stromal Activation in Rheumatoid Arthritis Pannus.

PET radioligands targeted to translocator protein (TSPO) offer a highly sensitive and specific means of imaging joint inflammation in rheumatoid arthritis (RA). Through high expression of TSPO on activated macrophages, TSPO PET has been widely reported in several studies of RA as a means of imaging synovial macrophages in vivo. However, this premise does not take into account the ubiquitous expression of TSPO.

The macrophage marker translocator protein (TSPO) is down-regulated on pro-inflammatory 'M1' human macrophages.

The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form of positron emission tomography (PET), as a means to detect and quantify inflammation in vivo. However, existing literature regarding TSPO expression on human activated macrophages is lacking, mostly deriving from brain tissue studies, including studies of brain malignancy, and inflammatory diseases such as multiple sclerosis.

Role of LIGHT in the pathogenesis of joint destruction in rheumatoid arthritis.

Aim: To characterise the role of substitutes for receptor-activator nuclear factor kappa-B ligand (RANKL) in rheumatoid arthritis (RA) joint destruction.

Methods: Synovial fluid (SF) macrophages isolated from the knee joint of RA patients were incubated with 25 ng/mL macrophage-colony stimulating factor (M-CSF) and 50 ng/mL LIGHT (lymphotoxin-like, exhibits inducible expression and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes) in the presence and absence of 25 ng/mL RANKL and 100 ng/mL osteoprotegerin (OPG) on glass coverslips and dentine slices. Osteoclastogenesis was assessed by the formation of multinucleated cells (MNCs) expressing tartrate-resistant acid phosphatase (TRAP) on coverslips and the extent of lacunar resorption pit formation on dentine slices.

Is vascular endothelial growth factor a useful biomarker in giant cell arteritis?

Objectives: To assess the performance of circulating vascular endothelial growth factor (VEGF) levels as a tool for diagnosing giant cell arteritis (GCA) in a cohort of patients referred for assessment of suspected GCA.

Methods: We selected 298 patients recruited to the multicentre study Temporal Artery Biopsy versus Ultrasound in diagnosis of suspected GCA (TABUL). In a random subset of 26 biopsy-proven GCA cases and 26 controls, serum from weeks 0, 2 and 26 was analysed for VEGF concentration using ELISA.

Co-expression of DKK-1 and Sclerostin in Subchondral Bone of the Proximal Femoral Heads from Osteoarthritic Hips.

Background: Osteoarthritis (OA) is a progressively degenerative joint disease influenced by structural and metabolic factors. There is growing evidence that subchondral bone is involved in both symptomatic and structural progression in OA. The Wnt pathway has been implicated in the progression of OA but the expression and function of the Wnt inhibitors, Dikkopf (DKK-1) and sclerostin (SOST), are unclear.

25-Hydroxy- and 1α,25-Dihydroxycholecalciferol Have Greater Potencies than 25-Hydroxy- and 1α,25-Dihydroxyergocalciferol in Modulating Cultured Human and Mouse Osteoblast Activities.

Despite differences in the phamacokinetics of 25-hydroxycholecalciferol (25(OH)D3) and 25-hydroxyergocalciferol (25(OH)D2) in man, the effects of these and their 1α-hydroxylated forms (1,25(OH)2D3 and 1,25(OH)2D2) on cellular activity of vitamin D-responsive cells have hardly been compared. We studied differences in the effects of these metabolites on cell number, gene transcription, protein expression and mineralisation of cultured human bone marrow-derived stromal cells (hBMSC) and rapidly mineralising mouse 2T3 osteoblasts. 50-1000 nM 25(OH) and 0.

Cellular and molecular mechanisms of bone damage and repair in inflammatory arthritis.

Bone remodelling relies on tightly controlled cycles of bone resorption and formation, mediated by osteoclasts and osteoblasts, respectively. The past two decades have seen a huge increase in our understanding of immune modulation and disruption of bone homeostasis in rheumatic diseases; identification of the molecular pathways responsible for accelerated bone loss in such conditions has given rise to potential novel therapeutic targets. Most recently, the role of microRNAs in inflammatory and noninflammatory bone loss raises the intriguing possibility that modification of cellular protein translation could also be a treatment strategy for bone damage.

The implementation of novel collaborative structures for the identification and resolution of barriers to pluripotent stem cell translation.

Increased global connectivity has catalyzed technological development in almost all industries, in part through the facilitation of novel collaborative structures. Notably, open innovation and crowd-sourcing-of expertise and/or funding-has tremendous potential to increase the efficiency with which biomedical ecosystems interact to deliver safe, efficacious and affordable therapies to patients. Consequently, such practices offer tremendous potential in advancing development of cellular therapies.

A Surgeon's guide to advances in the pharmacological management of acute Charcot neuroarthropathy.

Acute Charcot neuroarthropathy is a devastating condition and, its incidence is increasing. Currently, treatment consists of immobilisation and off-loading of the involved extremity. Outcomes are frequently poor and novel treatments are being sought urgently.

In vitro two-dimensional and three-dimensional tenocyte culture for tendon tissue engineering.

In order to examine the differentiation potential of the tenocytes expanded in our defined culture medium (reported previously) and the effect of sequential combination of the two culture conditions on human tenocytes, a two-dimensional and three-dimensional experimental approach was used. Human tenocytes were sequentially exposed to 1% fetal bovine serum (FBS) + 50 ng/ml platelet-derived growth factor-BB (PDGFBB ) + 50 ng/ml basic fibroblast growth factor (bFGF) for the first 14 days (expansion phase) followed by a further 14-day culture in the presence of 10 ng/ml transforming growth factor β-3 plus 50 ng/ml insulin-like growth factor 1, but in the absence of serum (differentiation phase). The results showed that by sequential treatment of human tenocytes maintaining a long-term two-dimensional tenocyte culture in vitro for up to 28 days was possible.

Development of a refined tenocyte expansion culture technique for tendon tissue engineering.

The aim of this study was to efficiently expand less differentiated tenocytes with minimum use of fetal bovine serum (FBS) for tenocyte-based tendon tissue engineering. To achieve this goal, human tenocytes were cultured in different concentrations of FBS and combinations of growth factors PDGF(BB), IGF-1 and bFGF. A number of growth factors were selected that could support tenocyte expansion at reduced differentiated state with minimum FBS usage.

Development of a refined tenocyte differentiation culture technique for tendon tissue engineering.

We have established that human tenocytes can differentiate in the absence of exogenous fetal bovine serum (FBS) but in the presence of insulin-like growth factor-1 (IGF-1) and transforming growth factor-β3 (TGF-β3). The extent of tenocyte differentiation was assessed by examining cell survival, collagen synthesis, cell morphology and expression of tenocyte differentiation markers such as scleraxis (Scx), tenomodulin (Tnmd), collagen type I (Col-I) and decorin (Dcn). Our results indicate that 50 ng/ml IGF-1 and 10 ng/ml TGF-β3 (in the absence of FBS) were capable of maintaining in vitro human tenocyte survival in 14-day cultures.

Proliferation and differentiation of human tenocytes in response to platelet rich plasma: an in vitro and in vivo study.

Platelet rich plasma (PRP) is the autologous plasma fraction with a platelet-rich cellular component which is enriched with a number of growth factors. Due to its availability and low cost, PRP has become an increasingly popular clinical tool as an alternative source of growth factors for various applications, for example, tendon regeneration but with limited success in clinical trials. The main objective of the current study was to determine whether activated PRP [i.

Improved human tenocyte proliferation and differentiation in vitro by optimized silk degumming.

Tendon disorders are common clinical conditions. Tendon tissue engineering provides a new approach for tendon repair by integrating engineered substitutes with their native counterparts. Silk is considered to be a promising candidate for tendon engineering because of its biological and mechanical properties.

TSG-6 inhibits osteoclast activity via an autocrine mechanism and is functionally synergistic with osteoprotegerin.

Objective: TSG-6 (the product of tumor necrosis factor [TNF]-stimulated gene 6) has a potent inhibitory effect on RANKL-mediated bone erosion. The aim of this study was to compare the activity of TSG-6 with that of osteoprotegerin (OPG) and to investigate its role as an autocrine modulator of cytokine-mediated osteoclast formation/activation. We also determined TSG-6 expression in inflammatory joint disease.

Role of the A20-TRAF6 axis in lipopolysaccharide-mediated osteoclastogenesis.

Bacterial lipopolysaccharide (LPS) has long been suggested as a potent inducer of bone loss in vivo despite controversial effects on osteoclast precursors. Recently, the role of the deubiquitinating protease A20 in regulating the LPS response in various organs was reported. In the present study, we investigated whether A20 is expressed in osteoclast cultures in response to RANKL or LPS and whether this protein plays a role in osteoclast formation and activation.

Interleukin-32 promotes osteoclast differentiation but not osteoclast activation.

Background: Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-gamma. IL-32 has the typical properties of a pro-inflammatory mediator and although its role in rheumatoid arthritis has been recently reported its effect on the osteoclastogenesis process remains unclear.

Methodology/principal Findings: In the present study, we have shown that IL-32 was a potent modulator of osteoclastogenesis in vitro, whereby it promoted the differentiation of osteoclast precursors into TRAcP+ VNR+ multinucleated cells expressing specific osteoclast markers (up-regulation of NFATc1, OSCAR, Cathepsin K), but it was incapable of inducing the maturation of these multinucleated cells into bone-resorbing cells.

Metal-on-metal hip resurfacing arthroplasty: a review of periprosthetic biological reactions.

Metal-on-metal hip resurfacing arthroplasty has undergone a recent resurgence as an alternative treatment option for young and active patients with significant osteoarthritis. The claimed advantages of metal-on-metal hip resurfacing arthroplasty include lower wear rate, preservation of bone stock for subsequent revision procedures, restoration of anatomic hip mechanics, and enhanced stability due to the larger diameter of articulation. A disadvantage, however, is that the metal-on-metal resurfacing releases large amounts of very small wear particles and metal ions.

Absence of lymphatics at the bone-implant interface: implications for periprosthetic osteolysis.

Background: Wear particles, found at the bone-implant interface surrounding a loose prosthesis, are commonly phagocytosed by macrophages. Wear particles and wear particle-containing macrophages are also found in regional lymph nodes draining arthroplasty tissues. The means by which wear particles are transported from arthroplasty tissues to lymph nodes is uncertain, as the presence or absence of lymphatic vessels in periprosthetic tissues has not been established.

Biological response to common surface bearings used in orthopaedics.

Wear particles are the most important cause of aseptic loosening of orthopaedic devices. To reduce the amount of particles generated from the conventional metal-on-polyethylene system, alternative bearings have been introduced. However, there are some concerns about so-called "adverse reactions" to these bearing surfaces.

Stimulation of osteoclast formation by inflammatory synovial fluid.

Peri-articular bone resorption is a feature of arthritis due to crystal deposition and rheumatoid disease. Under these conditions, the synovial fluid contains numerous inflammatory cells that produce cytokines and growth factors which promote osteoclast formation. The aim of this study was to determine whether inflammatory synovial fluid stimulates the formation of osteoclasts.

Osteolytic potential of triphenyl bismuth as an alternative contrast medium in acrylic bone cement.

Radiopaque cement containing barium sulfate causes significantly more bone resorption in vivo and in vitro than radiolucent cement. The aim of this study was to investigate the osteolytic potential of an alternative radiopaque agent, triphenyl bismuth (TPB). Bone cement particles containing various concentration of TPB (15 and 25 wt %) prepared by two methods, blending and dissolution, were added to monocytes in a bone resorption assay and the extent of lacunar resorption on dentine slices was determined.

Expression and function of TNF-family proteins and receptors in human osteoblasts.

We studied how tumor necrosis-factor (TNF)-family proteins interact with osteoblasts to resolve several controversial points. We measured expression of TNFs, TNF-receptors, and nonsignaling (decoy) TNF receptors in human osteoblasts derived from mesenchymal stem cells and in MG63 human osteosarcoma cells using unamplified mRNA screening, with secondary Western or PCR analysis where indicated, and studied the effects of TNFs on osteoblasts in cell culture. Expression of TNFs and receptors was similar in MG63 cells and osteoblasts.