Bone Abstracts

The G protein-coupled receptor, protease-activated receptor 2 (PAR2), is expressed by osteoblasts and required for normal skeletal growth and repair. Prostate cancer (PCa) cells commonly secrete proteolytic activators of PAR2 (including matriptase and kallikrein-related peptidase 4) and frequently form osteogenic metastases in bone. This study was undertaken to investigate the hypothesis that PAR2 activators released by PCa cells modulate osteo...

The biomineralization process is initiated inside matrix vesicles (MVs), with phosphate and calcium ions crystallizing as hydroxyapatite. This process is accomplished by the activities of several proteins, such as annexins (e.g. AnxV) that mediates Ca2+ influx into MVs and tissue-nonspecific alkaline phosphatase (TNAP), a phosphomonohydrolase that uses ATP and PPi as substrates. Dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS...

Constant remodeling of extracellular matrix (ECM) is a hallmark during physiological conditions, such as stem cell differentiation, embryogenesis and tissue repair. Matrix metalloproteinases (MMP) play a key role in these processes. MMPs, MMP-activator (EMMPRIN/CD147) and MMP-inhibitors (TIMPs and RECK) are responsible for bone matrix remodeling and, probably, determinate the level of its turnover. Mesenchymal stem cells derived from dental pulp are multipotent and have the ca...

Identifying novel molecules that enhance human skeletal (mesenchymal) stem cells (hMSC) differentiation into osteoblastic bone forming cells (OB), may lead to development of new bone anabolic drugs. We have identified Kix, a small molecule kinase inhibitor that enhanced ex vivo OB differentiation and reduced apoptosis of hMSC. We found that Kix targeted undifferentiated hMSC populations and not their differentiated progeny. In addition, Kix increased in vivo ...

Bone is a complex structure associating cells to an extracellular organic phase, including collagen and non collagenous proteins (NCPs), in close association with apatite mineral platelets. Although bone has given rise to extensive studies, the exact part played by NCPs in nucleating or inhibiting the mineral phase remains controversial. The present study aimed to better understand the functions of a major mineralizing protein, dentin matrix phosphoprotein 1 (DMP1), an acidic,...

The in vitro culture of calvarial osteoblasts from neonatal rodents remains an important method for studying the regulation of osteoblast function. Widespread use of transgenics has created a particular need for a reliable, simple method that allows the differentiation and bone-forming activity of mouse osteoblasts to be studied directly. We have established such a method and have identified key differences in optimal culture conditions between mouse and rat osteoblas...

In light of prolonged life expectancy, the need for biomaterials that govern bone regeneration increases. Improved bone regeneration and osseointegration can be achieved by funtionalizing implant materials. The extracellular matrix (ECM) affects differentiation of bone cells and is critical for bone regeneration. Here we assessed the role of the natural occurring bone ECM glycosaminoglycans (GAGs) hyaluronan (HA) and chondroitin sulfate (CS), and their sulfated derivatives, on...

Osteoclasts are produced by fusion of pre-osteoclasts derived from stem cells of the monocyte/macrophage lineage in the presence of receptor activator of NF-κB ligand (RANKL) produced by osteoblasts. The phytoestrogens; genistein and daidzein, which are isoflavones found in Leguminosae such as soybeans, are currently being investigated for prevention of postmenopausal osteoporosis. Some polyunsaturated fatty acids (PUFAs) have been shown to exert a bone protectiv...

RANKL induced osteoclastogenesis is mediated by several transcription factors such as NF-κB, AP-1 and Nfatc1. We have found that also cysteine proteinases are involved in the signaling pathway downstream RANK. Thus, cystatin C, Z-RLVG-CHN2 (the sequence of which is based upon one of the enzyme inhibitory domains in cystatin C) and the fungal molecule E-64 – inhibit RANKL induced mouse and human osteoclast formation in vitro (Strålberg et ...

Osteocytes differentiate from osteoblasts, are embedded in mineralised matrix and are critical regulators of bone remodelling. In vitro osteocyte models are limited to cell lines in monolayer, which do not represent their 3D environment in vivo. We have shown that osteoblasts in 3D gels differentiate along the osteocytic pathway. Since IGF1 regulates osteoblasts, and is involved in osteocyte response to mechanical loading, we hypothesised that IGF1 modulates ...