Unveiling the Bmp13 Enigma: Redundant Morphogen or Crucial Regulator?

Bone morphogenetic proteins are a diverse group of morphogens with influences not only on bone tissue, as the nomenclature suggests, but on multiple tissues in the body and often at crucial and influential periods in development

Unveiling the Bmp13 enigma: Redundant morphogen or crucial regulator?

Bone morphogenetic proteins are a diverse group of morphogens with influences not only on bone tissue, as the nomenclature suggests, but on multiple tissues in the body and often at crucial and influential periods in development. The purpose of this review is to identify and discuss current knowledge of one vertebrate BMP, Bone Morphogenetic Protein 13 (BMP13), from a variety of research fields, in order to clarify BMP13's functional contribution to developing and maintaining healthy tissues, and to identify potential future research directions for this intriguing morphogen. BMP13 is highly evolutionarily conserved (active domain >95%) across diverse species from Zebrafish to humans, suggesting a crucial function. In addition, mutations in BMP13 have recently been associated with Klippel-Feil Syndrome, causative of numerous skeletal and developmental defects including spinal disc fusion. The specific nature of BMP13's crucial function is, however, not yet known. The literature for BMP13 is focused largely on its activity in the healing of tendon-like tissues, or in comparisons with other BMP family molecules for whom a clear function in embryo development or osteogenic differentiation has been identified. There is a paucity of detailed information regarding BMP13 protein activity, structure or protein processing. Whilst some activity in the stimulation of osteogenic or cartilaginous gene expression has been reported, and BMP13 expression is found in post natal cartilage and tendon tissues, there appears to be a redundancy of function in the BMP family, with several members capable of stimulating similar tissue responses. This review aims to summarise the known or potential role(s) for BMP13 in a variety of biological systems

The acceptability, feasibility and impact of a lay health counsellor delivered health promoting schools programme in India: a case study evaluation.

BACKGROUND: Studies in resource-limited settings have shown that there are constraints to the use of teachers, peers or health professionals to deliver school health promotion interventions. School health programmes delivered by trained lay health counsellors could offer a cost-effective alternative. This paper presents a case study of a multi-component school health promotion intervention in India that was delivered by lay school health counsellors, who possessed neither formal educational nor health provider qualifications. METHODS: The intervention was based on the WHO's Health Promoting Schools framework, and included health screening camps; an anonymous letter box for student questions and complaints; classroom-based life skills training; and, individual psycho-social and academic counselling for students. The intervention was delivered by a lay school health counsellor who had attained a minimum of a high school education. The counsellor was trained over four weeks and received structured supervision from health professionals working for the implementing NGO. The evaluation design was a mixed methods case study. Quantitative process indicators were collected to assess the extent to which the programme was delivered as planned (feasibility), the uptake of services (acceptability), and the number of students who received corrective health treatment (evidence of impact). Semi-structured interviews were conducted over two years with 108 stakeholders, and were analysed to identify barriers and facilitators for the programme (feasibility), evaluate acceptability, and gather evidence of positive or negative effects of the programme. RESULTS: Feasibility was established by the high reported coverage of all the targeted activities by the school health counsellor. Acceptability was indicated by a growing number of submissions to the students' anonymous letter-box; more students self-referring for counselling services over time; and, the perceived need for the programme, as expressed by principals, parents and students. A minority of teachers complained that there was inadequate information sharing about the programme and mentioned reservations about the capacities of the lay health counsellor. Preliminary evidence of the positive effects of the programme included the correction of vision problems detected in health screening camps, and qualitative evidence of changes in health-related knowledge and behaviour of students. CONCLUSION: A task-shifting approach of delegating school health promotion activities to lay school health counsellors rather than education or health professionals shows promise of effectiveness as a scalable model for promoting the health and well being of school based adolescents in resource constrained settings

BMP13 Prevents the Effects of Annular Injury in an Ovine Model

Chronic back pain is a global health problem affecting millions of people worldwide and carries significant economic and social morbidities. Intervertebral disc damage and degeneration is a major cause of back pain, characterised by histological and biochemical changes that have been well documented in animal models. Recently there has been intense interest in early intervention in disc degeneration using growth factors or stem cell transplantation, to replenish the diseased tissues. Bone Morphogenetic Proteins (BMPs) have been approved for clinical use in augmenting spinal fusions, and may represent candidate molecules for intervertebral disc regeneration

BMP-13 Emerges as a Potential Inhibitor of Bone Formation

Bone morphogenetic protein-13 (BMP-13) plays an important role in skeletal development. In the light of a recent report that mutations in the BMP-13 gene are associated with spine vertebral fusion in Klippel-Feil syndrome, we hypothesized that BMP-13 signaling is crucial for regulating embryonic endochondral ossification. In this study, we found that BMP-13 inhibited the osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells (BM MSCs) in vitro. The endogenous BMP-13 gene expression in MSCs was examined under expansion conditions. The MSCs were then induced to differentiate into osteoblasts in osteo-inductive medium containing exogenous BMP-13. Gene expression was analysed by real-time PCR. Alkaline phosphatase (ALP) expression and activity, proteoglycan (PG) synthesis and matrix mineralization were assessed by cytological staining or ALP assay. Results showed that endogenous BMP-13 mRNA expression was higher than BMP-2 or -7 during MSC growth. BMP-13 supplementation strongly inhibited matrix mineralization and ALP activity of osteogenic differentiated MSCs, yet increased PG synthesis under the same conditions. In conclusion, BMP-13 inhibited osteogenic differentiation of MSCs, implying that functional mutations or deficiency of BMP-13 may allow excess bone formation. Our finding provides an insight into the molecular mechanisms and the therapeutic potential of BMP-13 in restricting pathological bone formation

Unveiling the Bmp13 Enigma: Redundant Morphogen or Crucial Regulator?

Bone morphogenetic proteins are a diverse group of morphogens with influences not only on bone tissue, as the nomenclature suggests, but on multiple tissues in the body and often at crucial and influential periods in development. The purpose of this review is to identify and discuss current knowledge of one vertebrate BMP, Bone Morphogenetic Protein 13 (BMP13), from a variety of research fields, in order to clarify BMP13's functional contribution to developing and maintaining healthy tissues, and to identify potential future research directions for this intriguing morphogen. BMP13 is highly evolutionarily conserved (active domain &#62;95%) across diverse species from Zebrafish to humans, suggesting a crucial function. In addition, mutations in BMP13 have recently been associated with Klippel-Feil Syndrome, causative of numerous skeletal and developmental defects including spinal disc fusion. The specific nature of BMP13's crucial function is, however, not yet known. The literature for BMP13 is focused largely on its activity in the healing of tendon-like tissues, or in comparisons with other BMP family molecules for whom a clear function in embryo development or osteogenic differentiation has been identified. There is a paucity of detailed information regarding BMP13 protein activity, structure or protein processing. Whilst some activity in the stimulation of osteogenic or cartilaginous gene expression has been reported, and BMP13 expression is found in post natal cartilage and tendon tissues, there appears to be a redundancy of function in the BMP family, with several members capable of stimulating similar tissue responses. This review aims to summarise the known or potential role(s) for BMP13 in a variety of biological systems.</p

Hyaluronan: its potential application in intervertebral disc regeneration

Bojiang Shen, Aiqun Wei, Divya Bhargav, Thomas Kishen, Ashish D DiwanOrthopaedic Research Institute, Department of Orthopaedic Surgery, St. George Hospital, The University of New South Wales, Sydney, AustraliaAbstract: Hyaluronan (HA) is a ubiquitous component of extracellular matrix in human tissues with diverse functions in skeletal biology. The biophysical properties of HA, such as high viscosity, elasticity and highly negative charge, make it useful in various therapeutic procedures. Although intra-articular administration of HA has been extensively used in the management of osteoarthritis (OA), there is a paucity of data on the clinical application of HA in intervertebral disc repair. This review discusses the biology and signaling mechanisms of HA, the pathophysiology of disc degeneration and summarises current evidence relating to the role of HA in cell phenotype maintenance, differentiation of chondrocytes, intervertebral disc cells and bone marrow stromal cells, and its application in tissue engineering. Based on recent advances in the clinical outcomes of OA treatment, HA has demonstrated potential as a bio-polymer filler, therapeutic agent and cell carrier in the management of intervertebral disc degeneration.Keywords: hyaluronan, cartilage, intervertebral disc, stromal cells, tissue engineering, back pai

Hyaluronan : its potential application in intervertebral disc regeneration

Hyaluronan (HA) is a ubiquitous component of extracellular matrix in human tissues with diverse functions in skeletal biology. The biophysical properties of HA, such as high viscosity, elasticity and highly negative charge, make it useful in various therapeutic procedures. Although intra-articular administration of HA has been extensively used in the management of osteoarthritis (OA), there is a paucity of data on the clinical application of HA in intervertebral disc repair. This review discusses the biology and signaling mechanisms of HA, the pathophysiology of disc degeneration and summarises current evidence relating to the role of HA in cell phenotype maintenance, differentiation of chondrocytes, intervertebral disc cells and bone marrow stromal cells, and its application in tissue engineering. Based on recent advances in the clinical outcomes of OA treatment, HA has demonstrated potential as a bio-polymer filler, therapeutic agent and cell carrier in the management of intervertebral disc degeneration

Bone morphogenetic protein-7 accelerates fracture healing in osteoporotic rats

Background: Osteoporosis is characterized by low bone mass, bone fragility and increased susceptibility to fracture. Fracture healing in osteoporosis is delayed and rates of implant failure are high with few biological treatment options available. This study aimed to determine whether a single dose of bone morphogenetic protein-7 (BMP-7) in a collagen/carboxy-methyl cellulose (CMC) composite enhanced fracture healing in an osteoporotic rat model. Materials and Methods: An open femoral midshaft osteotomy was performed in female rats 3 months post-ovarectomy. Rats were randomized to receive either BMP-7 composite ( n = 30) or composite alone ( n = 30) at the fracture site during surgery. Thereafter calluses were collected on days 12, 20 and 31. Callus cross-sectional area, bone mineral density, biomechanical stiffness and maximum torque, radiographic bony union and histological callus maturity were evaluated at each time point. Results: There were statistically significant increases in bone mineral density and callus cross-section area at all time points in the BMP-7 group as compared to controls and biomechanical readings showed stronger bones at day 31 in the BMP-7 group. Histological and radiographic evaluation indicated significant acceleration of bony union in the BMP-7 group as compared to controls. Conclusion: This study demonstrated that BMP-7 accelerates fracture healing in an oestrogen-deficient environment in a rat femoral fracture healing model to scientific relevance level I. The use of BMP-7 composite could offer orthopedic surgeons an advantage over oestrogen therapy, enhancing osteoporotic fracture healing with a single, locally applied dose at the time of surgery, potentially overcoming delays in healing caused by the osteoporotic state.7 page(s