Transforming growth factor-beta (TGF-β)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific. Additive, positive, negative, or synergistic effects are observed when TGF-β/BMP interacts with the pathways of MAPK, Wnt, Hedgehog (Hh), Notch, Akt/mTOR, and miRNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and β-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-β/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics.
A B S T R A C TStem cells are vital for regenerating and repairing the organs such as the heart, lungs, skin, germ cells and other tissues. But the characteristics of normal stem cells and the discovery of origin of leukemia have headed the scientist to the hypothesis that cancer may initiate from stem cell-like cells. Cancer stem cells are now thought to be responsible for cancer initiation, progression, metastasis, recurrence and drug resistance. There are some similarities and differences between CSCs and healthy stem cells in signaling pathways (Wnt/ β-catenin, Hh, Notch), epigenetic modifications, telomere maintenance, and degree of dependence on the stem cell niche, maintenance of multipotency and self-renewability of respective progenitor cells. Distinct and specific surface biomarker phenotypes can be used to distinguish CSC from other tumor cells and normal stem cells through single and combination of markers such as CD44, CD34 + CD38 × and CD133. Recently, miRNAs have been tried as a marker and therapeutic agents against cancers stem cell such as miR-34a, miR-199a, miR-181, miR-125b-2 and miR-128. However, targeting CSCs without harming their normal counterparts is an advantageous way in the design of novel therapies but many questions remain unknown.
Hydroxyapatite (HA) was extracted from bovine and human cortical bone by thermal decomposition process and was characterized using several analytical tools, including thermo-gravimetric analysis (TGA), X-ray diffraction analysis (XRD), X-ray fluorescence analysis (XRF), Flourier transformed infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Removal of organic matter from the bone was confirmed by TGA. XRD data confirmed that HA was the only crystalline phase when sintered at 950 °C. XRF analysis revealed that calcium and phosphorus were the main components and magnesium, sodium were the minor elements in which some trace elements (iron, potassium and zinc) were also present. FT-IR spectra of HA confirmed the presence of a carbonated group and the similarities to commercial HA. When HA were irradiated at 25kGy, there was no significant change of their properties. In vitro cytotoxicity of the HA powder were also evaluated and the samples showed no cytotoxic effect. These results suggested that HA derived from bovine and human bone by thermal decomposition has the potential to be used in bone tissue engineering.
Tissue Banking and Biomaterial Research Unit (TBBRU), the only tissue bank of Bangladesh, has been established to create an available supply of human tissue allografts for transplantation in Bangladesh. Since its establishment in 2003, TBBRU strictly follows the guidelines of tissue banking setup by the International Atomic Energy Agency, the European Association of Tissue Banks and the American Association of Tissue Banks. Though started serving from earlier, regular supply of tissue allografts from this bank were documented at the end of 2006. From January 2007 to December 2014, 3747 bones and 5772 amniotic sacs were collected from live tissue donors. During this period, 59,489 cc bone allografts and 23,472 pieces of amniotic membrane allografts were processed. In the same period, 58,483 cc bone allografts and 20,786 pieces membrane were supplied to different hospitals throughout the country on the basis of demand. The outcomes of the concerted efforts of tissue banking professionals and physicians were the restoration of health and hope of 3662 patients during the last 8 years.
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