Friday, August 3, 2012

Type III collagen may play a role in LSJL-inducible height growth

In the LSJL gene expression studies, no directly chondrogenic proteins were reported as being stimulated other than BMP-2 by 1.2 fold which is both a chondrogenic and osteogenic protein.  There are many proteins upregulated that are chondroinhibitory like ATF-3 and EGR-1.  Asporin inhibits TGF-Beta but it also is upregulated by TGF-Beta as part of a negative feedback loop indicating a possible increase in TGF-Beta levels.  Several chondrogenic and not osteogenic ECM proteins were upregulated by LSJL like hyaluronic acid and chondroitin.  MMP-3 is involved in the release of TGF-Beta from the TGF-Beta compound.  Thus, the active form of TGF-Beta can be increased by MMP-3 even if the total levels of TGF-Beta are not increased.  In addition to chondrogenic ECM proteins and an increase in the active form of TGF-Beta playing a role in chondroinduction by LSJL, type III collagen may play a role as well.

Marrow stimulation techniques.

"The AMIC (autologous matrix induced chondrogenesis) technique was developed to enable treatment of larger defects by the application of a collagen Type III/I membrane[procollagen type III, alpha 1 is upregulated 3.6 fold by LSJL], in particular when cell-engaged procedures such as ACT cannot be used for financial reasons or because it is not indicated. AMIC seems to be particularly suitable for treating damaged retropatellar cartilage, which is an advantage because these defects can be hard to treat with standard microfracturing alone."<-This is sort of what we're doing with LSJL by altering the matrix.  It should be noted this is for knee repair and not the epiphyseal bone marrow.  Also AMIC involves microfracturing to get bone marrow but the epiphyseal bone marrow already has the bone marrow and so microfracture is not needed.  It also already has type I collagen.

Interplay between local versus soluble transforming growth factor-Beta and fibrin scaffolds: role of cells and impact on human mesenchymal stem cell chondrogenesis.

"A collagen-type I/III (Col-I/III) matrix, human recombinant transforming growth factor-beta (TGF-β) protein, and fibrin hydrogel (FG) combined to a biphasic construct provided sufficient long-term TGF-β support to drive in vitro chondrogenesis of human mesenchymal stem cells (hMSC). Here we ask whether FG and Col-I/III can both retain TGF-β, describe the influence of cell seeding on TGF-β release, and compare the molecular path of hMSC chondrogenic differentiation under soluble versus local TGF-β supply. Release of growth factor from scaffolds augmented with increasing amounts of TGF-β was analyzed over 7 days and chondrogenesis was assessed over 42 days. Low TGF-β release rates from Col-I/III as opposed to higher release from FG indicated that both molecules retained TGF-β, with Col-I/III being the superior storage component. Cell seeding enhanced TGF-β retention in FG by about threefold and almost stopped release beyond 24 h. TGF-β remained bioactive and supported MSC chondrogenesis without impairing the amount of proteoglycan and collagen-type II deposition per cell and per construct compared to standard scaffold-free MSC pellets supplied with soluble TGF-β. Local TGF-β, however, mediated lower cell content, less collagen-type X relative to collagen-type II deposition and no matrix metalloproteinase-13 up-regulation[local TGF-Beta meant more TGF-Beta available so maybe continuous TGF-Beta won't help you grow taller, LSJL is more like transient TGF-Beta as it is performed intermittently]. In conclusion, cells quickly halted release of local TGF-β from FG, turning FG and Col-I/III into attractive TGF-β repositories capable to drive full hMSC chondrogenesis, but via a modulated differentiation pathway."

In the study Sustained expression of proteoglycans and collagen type III/type I ratio in a calcified tendinopathy model.,  an increase in type III to type I collagen ratio resulted in an increase in chondrogenesis in the tendon.  Since LSJL upregulated type III collagen to a greater amount than type I collagen then the ratio increases.  

Hypoxia-inducible factor 1alpha inhibits the fibroblast-like markers type I and type III collagen during hypoxia-induced chondrocyte redifferentiation: hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III collagen in the hypoxia-inducible factor 1alpha-dependent redifferentiation of chondrocytes., states that hypoxia decreases type I and type III collagen expression and hypoxia is an important chondroinductive compound.  However, this might be part of a negative feedback mechanism and might not be a mark against type III collagen being height promoting.

According to the grant TYPE III COLLAGEN GENE EXPRESSION IN CARTILAGE,  type III collagen is produced in pre-chondrogenic cells.  So the type III collagen upregulation may be a sign that LSJL induced mesenchymal chondrogenesis and thus new growth plate formation in the epiphyseal bone marrow.

The increase in the Type III collagen ratio may be part of the chondroinductive mechanism's of LSJL and thus may be height promoting.  Alternatively, the increase in type III collagen may be a sign of mesenchymal chondrogenic(new growth plate forming) differentiation.


Evidence for an extensive collagen type III proximal domain in the rat femur: II. Expansion with exercise

"Using the rat model, 1.5-month-old females were divided into four weight-matched groups, exercised short-term (6 weeks, Es, n = 20) and long-term (14 weeks, EL, n = 10) by access to monitored running wheels, and corresponding “sedentary” control"

"Sharpey’s fibres are extensions of the periosteum attaching tendons and ligaments to bone."

"they form a pervasive polarised system of birefringent, poorly mineralised, fibres that stain with collagen type III antibody"

"Endochondral growth (indicated by bone length) was not affected by running. However, intramembranous growth (indicated by bone width) did change."  Although there did seem to be a statistically insignificant increase in bone length between both short and long term exercise groups and the controls.  About .3mm.

Exercise increased the number of Type III collagen fibers.

14 comments:

  1. Does the Type III collagen upregulation also apply for alkoclar's idea for new growth plate formation, assuming that his idea is the FGF-2&CNP?

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    1. Type III collagen upregulation was mostly to prove that LSJL does upregulate chondrogenic genes according to the gene expression study. Type III collagen was produced by pre-chondregenic cells. Our goal is to prove that LSJL induces mesenchymal chondrogenesis.

      There are least two proteins required to induce height growth because of negative feedback but these proteins can vary. FGF-2 & CNP, Sox9 & Col2A1, TGF Beta & NO. You basically need a Cyclin D1 stimulator and a chondrogenic inducer(something that stimulates Sox9 transcription). Scientists also test for Aggrecan so ECM genes might be necessary as well.

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  2. Hey glad for the new post.
    Sorry it is way too scientifical language, I hardly understand anything from it.

    Could you please explain the following, because I didn't get it from the text:

    1.)what is Type III collagen
    2.) how do I mix it with Lsjl?

    thank you!

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    1. This is possible proof that LSJL induced mesenchymal chondrogenesis in the LSJL studies as prechondrogenic cells produce Type III collagen. Other cells produce Type III collagen too but if osteo-cells were producing the Type III collagen why weren't they producing type I collagen as well?

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  3. Hi Tyler,
    We know that epiphyseal growth plates, located in the secondary ossification center, don't fuse after puberty. Thanks to this fact we can perform LSJL. But after gain about 4 cm (1 1/2") nobody get results. Do LSJL cause ephipyseal growth plates fusion?

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    1. That was the original belief but then we discovered that epiphyseal growth plates do fuse but you can form new growth plates via inducing chondrogenic differentiation in the epiphyseal bone marrow. LSJL induces bone modeling which likely makes it more difficult for fluid flow to reach the unloaded epiphysis. So there's a need to increase the load over time. I'm working on this. Loading at 200 seconds per day now.

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    2. That's a good theory of why LSJL stops working after a certain point...Tyler Can you answer this question?

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  4. @ franscesco ...how do you know that after 1 1/2 inches nobody gets height?
    first of all tell us that DID YOU GET POSITIVE RESULTS FROM LSJL PLEASE?
    what is your age and LSJL routine?
    please let us know ---->this may encourage us a lot
    keep it up boys...
    i love this site..

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    1. Anonymous, I learned this from LSJL.info by user Osteoblast (http://lsjl.freeforums.org/viewtopic.php?t=502&p=3841). I have not started LSJL routine, because I have not yet reached 70 lbs dumbbells. However, I will start soon, I will not hesitate to say it and post my results on this blog and LSJL.info. I'm 23 years old.

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  5. Tyler what do you think about this? http://www.schweizerbart.de/papers/anthranz/detail/69/76476/Longitudinal_shrinkage_in_lower_legs_Negative_grow

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    1. I'm a bit scared of a negative growth

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    2. but whats the point of this? that after you plates are closed you shrink 2-3 mm per year?

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    3. According to this study at least in the tibia, but overall height increase a little bit , because i have read many times that concripts enlisted in the army at 18 are a little bit taller an year after. Sorry for bad english and i would like to know what tyler think about this.

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  6. Hi tyler i have been using this website for three months
    i have a suggestion ...
    regarding LSJL you should update all technique in simple steps
    1) starting and duration
    2) any updates

    3) ESP TYPE OF FOOD WHICH WE SHOULD EAT AND AVOID DURING LSJL like milk smoking etc

    In this way we can get LSJL volunteers results in better and quick way...

    I KNOW YOU HAEV MENTIONED EVERYTHING IN DETAILS IN DIFFERENT BLOGS AND LSJL FORUM

    BUT

    please mention it in single post with all foods and stuff in simple one line or least words..

    thanks

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