Me: Let me first just post the conclusion first from the researchers..
“In the current study we hypothesized that increased expression of both BMP2 and VEGF-A to a tissue-engineered construct seeded with MSCs would augment osteogenesis and angiogenesis. We focused onVEGF-A as this is the major proangiogenic isoform.21 Interestingly, we found that codelivery of these growth factors requires optimization as VEGF potently inhibited BMP2 expression. Conversely, BMP2 had little effect on VEGF expression. The inhibition of BMP2 expression by VEGF occurred at the RNA level, and VEGF inhibited the expression of endogenous BMP2 as well as adenovirally delivered BMP2. The latter finding suggests that VEGF inhibition occurs independently of the BMP2 promoter since the adenoviral gene expression was driven by a constitutively active promoter. Taken together, our findings suggest that approaches utilizing concurrent delivery of growth factors require optimization of growth factor concentration.”
Implications for height increase technology: I think it is very clear that unlike what I and many other researchers thought previously we can’t just combine growth factors together without looking at concentration, density, and percentages in mixtures and expect such growth factor compounds to work synergistically. While the VEGF may have bone modulating properties, when combines with BMPS it may inhibit BMPs and that may be the real way it controls bone growth in vivo. In the paper they hypothesis from teh results that it may be VEGF which is one of the causes for endochondral ossification and caus ethe vascularization of the cartilage for real bone cell stacking leading to height increase. If this is the case, then VEGF operates almost in the opposite effect as the Chondromodulin we researched in recent previous posts. Besides decreasing the estrogen levels in the teenagers body or pluggin up the estrogen receptor alpha and beta in the growth plates, we might be able to also manipulate chondromodulin and VEGF to increase and decrease respectively to slow down the ossification coversion process of what is left of the cartilage in the growth plates.
Also, we know that BMP-2 leads to chondrogenesis as well as osteogenesis and we are focused on differentiating those MSCs towards chondrocytes. If we can help in anyway to prevent the MSCs from differentiating into the osteoblasts and only allow for conversion into chondrocytes and chondroblasts we just might be able to eventually cause enough cells in the intermedullary cavity of the epiphysis to result in newly formed growth plates from chondrocyte aggregation. With enough time, maybe even the cell apoptosis and formation cycle using osteclasts to remove old cell waster may allow for an entire section of the bone to be replaced by chondrocytes. This would indeed prove the ultimate path towards growth plate regeneration and validate the theory on why LSJL would even work to make people taller.
From the paper…
“…several factors limit this technique from becoming routine in clinical practice. One of the biggest obstacles to the use of tissue-engineered constructs in reconstruction of tissue defects is the lengthy culture and manufacturing periods required by conventional techniques. For instance, the synthesis of a tissue-engineered bone construct usually requires a 6–12 week culture and seeding period.”
“The use of exogenous growth factors may be a means by which tissue-engineered construct synthesis and vascularization can be accelerated. Bone morphogenetic proteins (BMPs) may be a method by which osteogenesis can be enhanced in a tissue-engineered bone construct since these growth factors are known to promote osseous repair in endochondral and membranous bones.12–14 BMPs are critical for successful fracture repair and bone development, and exogenous delivery of BMP can induce bone formation in critical-sized bone defects.15,16 Thus, genetic manipulation of cell-seeded MSC constructs with BMP may represent a viable method to accelerate or augment bone deposition
Similarly, delivery of angiogenic growth factors, such as vascular endothelial growth factor (VEGF), may be a means by which vascular ingrowth can be augmented since these molecules regulate angiogenesis. Further, several studies have shown that angiogenesis and osteogenesis are synergistic.17–20 Thus, genetic modification of cell seeded constructs with VEGF may augment vascular ingrowth and osteogenesis in a tissue-engineered construct, thereby accelerating construct synthesis and angiogenesis.”
From Pubmed study link HERE… (This link has the full article)
Vascular Endothelial Growth Factor Inhibits Bone Morphogenetic Protein 2 Expression in Rat Mesenchymal Stem Cells
Abstract
Introduction: While several studies report that bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) can act synergistically to improve bone tissue engineering, others suggest that VEGF inhibits osteogenesis. The purpose of these experiments was therefore to evaluate the effect of dual transfection of these growth factors and potential mechanisms of interaction on gene expression and osteogenesis in vitro and in vivo. Methods: Marrow-derived mesenchymal stem cells (MSCs) were exposed to recombinant VEGF protein or transfected with adenoviruses encoding BMP2,VEGF, or LacZ in a variety of ratios. Alterations in gene and protein expression in vitro as well as bone formation in vivo were assessed. Results: MSC exposure to AdV-VEGF or recombinant VEGF inhibitedBMP2 mRNA expression, protein production, and MSC differentiation. Coculture experiments revealed that BMP2 suppression occurs through both an autocrine and a paracrine mechanism, occurring at the transcriptional level. Compared to controls, cotransfection of VEGF and BMP2 transgenes prevented ectopic bone formation in vivo. Conclusion: VEGF is a potent inhibitor of BMP2 expression in MSCs, and supplementation or overexpression of VEGF inhibits osteogenesis in vitro and ectopic bone formation in vivo. Strategies to utilize MSCs in bone tissue engineering therefore require careful optimization and precise delivery of growth factors for maximal bone formation.
