BMP3 suppresses osteoblast differentiation of bone marrow stromal cells via interaction with Acvr2b

Enhancing bone morphogenetic protein (BMP) signaling increases bone formation in a variety of settings that target bone repair. However, the role of BMP in the maintenance of adult bone mass is not well understood. Targeted disruption of BMP3 in mice results in increased trabecular bone formation, whereas transgenic overexpression of BMP3 in skeletal cells leads to spontaneous fracture, consistent with BMP3 having a negative role in bone mass regulation. Here we investigate the importance of BMP3 as a mediator of BMP signaling in the adult skeleton. We find that osteoblasts (OBL) and osteocytes are the source of BMP3 in adult bone. Using in vitro cultures of primary bone marrow stromal cells, we show that overexpression of BMP3 suppresses OBL differentiation, whereas loss of BMP3 increases colony-forming unit fibroblasts and colony-forming unit OBL. The ability of BMP3 to affect OBL differentiation is due to its interaction with activin receptor type 2b (Acvr2b) because knockdown of endogenous Acvr2b in bone marrow stromal cells reduces the suppressive effect of BMP3 on OBL differentiation. These findings best fit a model in which BMP3, produced by mature bone cells, acts to reduce BMP signaling through Acvr2b in skeletal progenitor cells, limiting their differentiation to mature OBL. Our data further support the idea that endogenous BMPs have a physiological role in regulating adult bone mass.     

Coral reefs studies and threats in Malaysia: a mini review

Coral reefs in Malaysia are about 4,006 km² with over 550 species contributed to nation’s economy. Coral reefs studies and threats in Malaysia have been reviewed briefly. Perspectives are addressed as coral reefs studies, threats, gaps and future studies. Coral reefs in Malaysia are being damaged at an increasing rate where it faces natural and anthropogenic stresses. Excellent summaries are available in terms of coral reefs cover throughout Malaysia however scarce in terms of qualitative, quantitative and biogeographical data. There are also limited studies on heavy metals concentration in corals skeleton studies. Poor to fair conditions of coral reefs in Peninsular Malaysia is due to increases of sedimentation and tourism impacts. Overfishing and fish blasting were main threats of coral reefs damage in Sabah. In Sarawak, coral reefs are threatened by high sedimentation and sand mining. The 1998–1999 bleaching event also affected coral reefs in Malaysia due to climate change. Gaps in coral reefs studies can be completed by continuous collaborations between local and international researchers as well as research by local universities. Economic valuation, policy analysis and community participation are directions in future coral reefs studies in Malaysia. Future studies are to understand effects of management on coral reefs health and impact of pollution on coral reefs growth with a standard coral reefs methodology. Established legal systems to reduce threats received by coral reefs are also need to be introduced. Role of science-driven management with community participation and media mass are also gaps to be highlighted in future studies.     

Serum lipid levels and bone mineral density in Greek postmenopausal women

Contradictory results have been reported regarding a relationship between serum lipid levels and bone mineral density. The purpose of this study was to further investigate a possible relationship between those parameters in Greek postmenopausal women. A total of 591 patients followed at a tertiary hospital were examined for seven different lipid factors in relation to dual-emission X-ray absorptiometry measurements at the lumbar spine. Lipoprotein-a was the only lipid measurement that univariately showed an almost significant trend of association with bone mass category (analysis of variance [ANOVA] p value 0.062 for Ln(Lipoprotein-a)). In multiple regression, it was noted that a non-significant negative trend of association of high density lipoprotein (HDL) cholesterol and Apolipoprotein AI with lumbar T-score (p value 0.058 and 0.075, respectively). In age subgroup analysis, Lipoprotein-a and Ln(Lipoprotein-a) presented a negative correlation with lumbar T-score for women with age ≥ 53 years (p value 0.043 and 0.070, respectively), while a negative correlation of HDL and Apolipoprotein AI levels with lumbar T-score remained in women with age < 53 years (p value 0.039 and 0.052, respectively). The findings do not support a strong relationship between lipid levels and bone mass measurements.     

Evaluating phylogenetic tree shape: two modifications to Fusco & Cronk's method.

Measurement of the degree of asymmetry in phylogenetic trees is important because a tree's shape reflects the process by which it has grown. For example, highly asymmetric trees are evidence that species have had different potential for diversification. Of the tree shape measures in the literature, that proposed by Fusco & Cronk (J. theor. Biol.175, 235-243) appears to be particularly useful, because it does not require fully-resolved trees whose terminals are of equal taxonomic rank. The value of the asymmetry or imbalance at a node is intended to be independent of the number of species ultimately descended from the node. In this paper, however, we point out that the value does depend upon species number. We propose two modifications that remove the dependency and so increase the measure's usefulness. We illustrate the use of the modified measures, which are implemented in a freely-available program, MESA.     

Traveling waves in a simple population model involving growth and death

The structure of solutions to a simple spatially dependent population model involving growth and death is investigated. Two forms of motility of the population are considered: (1) random motion only modeled by a Fickian law, and (2) a directed component of motion (chemotaxis), included in addition to the random motion. Under certain growth conditions a traveling wave of constant speed is approached. This speed can be increased by the addition of the chemotaxis with a corresponding increase in the asymptotic population. Development of initial conditions into a wave is illustrated numerically.     

Heparan sulfate proteoglycans retain Noggin at the cell surface: a potential mechanism for shaping bone morphogenetic protein gradients.

Bone morphogenetic proteins (BMPs) are expressed broadly and regulate a diverse array of developmental events in vivo. Essential to many of these functions is the establishment of activity gradients of BMP, which provide positional information that influences cell fates. Secreted polypeptides, such as Noggin, bind BMPs and inhibit their function by preventing interaction with receptors on the cell surface. These BMP antagonists are assumed to be diffusible and therefore potentially important in the establishment of BMP activity gradients in vivo. Nothing is known, however, about the potential interactions between Noggin and components of the cell surface or extracellular matrix that might limit its diffusion. We have found that Noggin binds strongly to heparin in vitro, and to heparan sulfate proteoglycans on the surface of cultured cells. Noggin is detected only on the surface of cells that express heparan sulfate, can be specifically displaced from cells by heparin, and can be directly cross-linked to a cell surface proteoglycan in culture. Heparan sulfate-bound Noggin remains functional and can bind BMP4 at the plasma membrane. A Noggin mutant with a deletion in a putative heparin binding domain has reduced binding to heparin and does not bind to the cell surface but has preserved BMP binding and antagonist functions. Our results imply that interactions between Noggin and heparan sulfate proteoglycans in vivo regulate diffusion and therefore the formation of gradients of BMP activity.