.TAK-778 induces osteogenesis in ovariectomized rats via an estrogen receptor-dependent pathway.
"TAK-778, a derivative of ipriflavone, has been shown to induce bone growth both in vitro and in vivo. TAK-778 can enhance osteoblast differentiation of human bone marrow cells via an estrogen receptor (ER)-dependent pathway. We tested if TAK-778 induced osteogenesis via an ER-dependent pathway using an ovariectomized (OVX) rat model. Two weeks after test animals underwent ovariectomy, TAK-778 and/or tamoxifen was administered orally over 3 months. Vehicle-treated and sham-operated rats served as controls. The bone mineral density (BMD) of the lumbar vertebrae and sagittal two-dimensional images of the L3 vertebral body were measured. In addition, bone formation rates (BFR) and serum calcium and osteocalcin levels were measured. TAK-778 significantly increased BMD, serum calcium and osteocalcin levels, and BFR when compared to that of the vehicle-treated group[osteocalcin is a byproduct of osteoblasts so it is used to measure osteoblast levels]. However, tamoxifen, a well-known ER antagonist, clearly inhibited the increase in these parameters induced by TAK-778. Treatment with TAK-778 increased the structure model index, bone volume/tissue volume[volume = length * width * HEIGHT], and trabecular thickness parameters and decreased the trabecular separation/spacing in OVX rats. Tamoxifen suppressed these effects when administered in combination with TAK-778. Taken together, the present study showed that TAK-778 enhanced bone formation in OVX rats and that this effect was dependent on an ER-mediated pathway."
Now, post fusion you don't need to worry about inhibiting osteoclast activity. Histological evidence of fusion was established in the paper Histology of Epiphyseal Union in Mammals. Exactly, when fusion occurs is unclear. X-rays will only tell you if you are not fused and not if you are. The thin line apparent on most x-rays on bones could be epiphyseal scarring or it could be a hyaline cartilage growth plate line remnant. X-rays are not three dimensional and parts of the bone fuse at different rates so unfused portions of the bone could be unfused. You should not take extra osteoclast inhibitors unless you are fairly confident that you do not have any leftover cartilage in your bone. If you aren't trying to grow by a cartilage intermediary like via endochondral ossification then trying to grow by osteoblasts is possible. If you can get MSCs to differentiate into osteoblasts on the subchondral plate and deposit new bone there you will grow taller.
Alfalfa can also up mechanosensitivity which will help you grow taller by endochondral ossification. It's unclear whether the encouraged differentiation of MSCs into osteoblasts will compete with the target goal of differentiating into chondrocytes by means of LSJL.
"TAK-778 stimulates proliferation of uncommitted mesenchymal C3H10T1/2 cells without inducing differentiation"<-so TAK-778 increases stem cell proliferation which is very good. Maybe the Estrogen agonist can block the induction into an osteoblastic lineage and Alfalfa can solely be used to increase stem cell proliferation
"Cell secretory activities were stimulated by TAK-778. The presence of tamoxifen alone did not affect the synthesis activity of cells."<-The anabolic benefits of Alfalfa can occur even when tamoxifen(an estrogen receptor inhibitor) is inhibiting the differentiation of stem cells into osteoblasts.
So an Estrogen Receptor blocker and Alfalfa in conjunction with LSJL may help you grow taller. The effects of estrogen receptor blockers will have to be studied further to make sure that the good effects on height growth outweigh the bad.
Ipriflavone modulates IGF-I but is unable to restore bone in rats.
"Seventy-two, 90 day-old Sprague-Dawley rats were divided into six groups (sham two groups; ovariectomized four groups). Thirty-five days from the date of surgery, one sham and one ovx group were killed to verify the occurrence of bone loss. The remaining four groups were sham, ovx, ovx + ipriflavone (100 mg[sol ]kg body weight per day), or ovx + 17beta-estradiol (10 microg[sol ]kg body weight daily) for a period of 65 days. Ipriflavone was ineffective in restoring bone density and unlike estrogen did not prevent bone resorption as evidenced by increased urinary excretion of hydroxyproline and serum tartrate-resistant acid phosphatase activity. Ipriflavone increased the expression of IGF-I in the femur."
Increasing IGF-1 expression is very good because IGF-1 determines the maximum size chondrocytes achieve during chondrocyte hypertrophy so maybe Ipriflavone can have positive benefits during puberty. It's just TAK-778 that inhibits bone resorption which is vital during endochondral ossification. Normal ipriflavone does not inhibit bone(and chondrocyte matrix) absorption.
The rats in the control group had a shorter left femur(by .10 cm) than the other groups which is unusual considering the rats were 90 days old. The estrogen treated group had a shorter left femur length by 0.07 cm then the OVX group and the Ipriflavone treated group. Maybe Ipriflavone reproduces the good effects of estrogen while taking out the bad. The rats were controlled for body weight and not length so the control group may have just had denser bones. But the rats did not have their ovaries removed until after the experiment had begun.
So there is likely an affect on height growth as a result of an ovareictomy. The estrogen treated group was taller than the control group by 0.03 cm despite having higher estrogen levels than the control group. So the ovaries may have height reducing effects independent of increasing serum levels of estrogen.
Ipriflavone may help you maintain your bone density if you decide to embark on a regime that inhibits estrogen.
The effect of oral ipriflavone on the rat mandible during growth.
"The aim of this study was to examine the effect of IF on rat mandibles during the growth stage. Thirty-two 5-week-old Wistar male rats were divided into four groups. The control group was fed a standard diet, group A received a low calcium diet (calcium content 30 per cent of the standard diet) for 6 weeks, and the other two groups were fed a low calcium diet for 3 weeks and then a standard diet without IF (group B) or with IF (group C) for 3 weeks. In addition, distilled water was provided for all groups. For mandibular length, the control group showed a significantly higher value than groups A and B, while group C demonstrated a significantly higher value than group A. In addition, the control group and group C showed significantly higher values for mandibular ramus height than group A). However, bone mineral density in trabecular bone was significantly higher in the control group than in the other groups and bone mineral density in cortical bone was significantly higher in the control group than groups A, B and C . Bone mineral density in both trabecular and cortical bone was significantly higher in group C than in groups A and B. These results indicate that complete recovery from calcium deficiency to the level of the control group may not be attainable, even though IF enhances calcium absorption to act on bone cells and promote bone construction."
This study shows that calcium deficiency decreases height. Now I don't recommend inducing calcium deficiency, I'm just saying that extreme levels of calcium may inhibit osteoclastic activity which is an important part of the height growth process. Some may point out that ipriflavone is a phytoestrogen, however estrogens are not bad unless in extremely high or low levels. And ipriflavone does not seem to have the height reducing effects that estrogen may have in too high doses.
Supplementing with ipriflavone during development can increase height by increasing IGF-1 expression. The usage of TAK-778 is unknown as it inhibits bone resorption which is an important part of the height growth process.
Ipriflavone does seem to have a beneficial effect on chondrocytes which may have a further benefit on LSJL.
Effects of ipriflavone and its metabolites on human articular chondrocytes cultivated in clusters.
"Ipriflavone (IP) is an isoflavone derivative that was suggested to have bone-sparing effects in post-menopausal and senile osteoporosis. A moderate stimulatory effect of IP and its metabolites on proliferation of osteoblastic cells was reported in rat osteoblastic osteosarcoma cell line. We investigated the effects of different concentrations (0, 1, 10 and 100 micrograms/ml) of IP and its metabolites (MET I, II, III and V) on the incorporation of [3H] thymidine and production of proteoglycans (PG) and type II collagen (COL II) by human articular chondrocytes[articular chondrocytes are pretty similar to growth plate chondrocytes except that they don't undergo the final stages of endochondral ossification] during a 12-day period, in a three-dimensional chondrocyte culture model. [3H]thymidine uptake was measured in chondrocyte clusters, and specific PG and COL II radioimmunoassays were performed every 4 days on the culture medium and cell clusters. Incubation with IP or its metabolites did not affect [3H]thymidine uptake regardless of the dose. PG released into the culture medium and PG cluster content rose significantly in presence of IP (1, 10 and 100 micrograms/ml)[Alfalfa increases proteoglycan content which could help you grow taller]. MET I increased PG release in culture medium (10 and 100 micrograms/ml) and PG cluster content (100 micrograms/ml). MET II has no effect on PG production. MET III increased PG in culture medium (100 microgram/ml) but did not influence PG cluster content while MET V (100 micrograms/ml) increased both PG release in culture medium and PG cluster content. COL II release in culture medium and COL II cluster content were significantly increased in presence of IP[Alfalfa increases the release of Type II Collagen which increases growth plate quality] (10 and 100 micrograms/ml), MET III (1, 10 and 100 micrograms/ml) or MET V (100 micrograms/ml). MET I and II did not significantly affect COL II production."
So it would seem that Ipriflavone could help you grow taller during puberty by increasing your growth plate quality by inducing chondrocytes to secrete more Collagen II and Proteoglycans. In addition, this would be beneficial if you are already growing taller with LSJL. Alfalfa also increases stem cell proliferation and IGF-1 expression two anabolic activities which will help you grow taller. Alfalfa also allows you to inhibit estrogen with less negative consequences.
Tamoxifen may induce apoptosis in growth plate chondrocytes. Apoptosis is a necessary part of endochondral ossification so that is not necessarily a bad thing. This product may have Tamoxifen in it but ingredients can not be validated: Redefine Nutrition Pct Revolution, 60-Count
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