This study shows that the 2nd step in what we had proposed in previous posts about how to induce cartilage regrowth has already been tested, experimented, and being shown to be successful. From PubMed study “Rejuvenation of periosteal chondrogenesis using local growth factor injection.“
Analysis And Interpretation: There are two studies we will be looking at here. First we must remember that for the overall thickness of a outer cortical bone layer of a long bone to stay constant after physical maturity, the rate at which the inner layer of the bone to dissolve and get absorbed into the marrow must equal the rate at which the layer of the outer of the bone, next to the periosteum must be the same. If not, the long bone with either get thicker or thinner. We remember that there is constant appositional growth of the periosteal layer of the bone even in adulthood.
For the 1st article…
This shows that if we take the growth factors TGF-Beta1 and IGF-1 and injected them into the subperiosteal layer of the periosteum even in aged mammales, it would result in the periosteum restoring its chondrogenetic abilities like when it was younger. The cambium cells in the lower layer of the periosteum which is what really divides and forms new bone thickness increased in number and in proliferation ability. This is in vitro but I can’t see why the same results would not occur in vivo.
All I can say is to read the really short summary/abstract and you will see that this experiment shows what may be the first easy to implement way to increase chondrocytes in the right area. This would be a way to explain the occasional results we find in people who do the LSJL method. Maybe the dynamic loading laterally manages to cause the cambium layer to form more growth factors, speficially the TGF-1 and cause it to increase in thickness on the top edges of the epiphysis which leads to overall height increase.
For the 2nd article…
The researchers state very clearly that ” The findings of this study indicate that exposure to TGF-beta1 has a stimulatory effect on periosteal chondrogenesis“. As for the correct dosage for maximum increase in cartilage formation and chondrocyte cell numbers, the researchers stated it was at 100 ng/mL of TGF-beta1 for thirty minutes. So if you inject a high level of TGF-beta 1 at short bursts of time, it causes the periosteal cambium cells to go through chondroogenesis. Not only cartilage, but the Type II collagen content and sulfate incorporation ability increased as well.
Osteoarthritis Cartilage. 2009 Jun;17(6):723-34. doi: 10.1016/j.joca.2008.10.011. Epub 2008 Nov 6.
Rejuvenation of periosteal chondrogenesis using local growth factor injection.
Source
Department of Orthopedic Surgery, Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. gregory.reinholz@mayo.edu
Abstract
OBJECTIVE:
To examine the potential for rejuvenation of aged periosteum by local injection of transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-1 (IGF-1) alone or in combination to induce cambium cell proliferation and enhance in vitro periosteal cartilage formation.
METHODS:
A total of 367 New Zealand white rabbits (6, 12, and 24+ month-old) received subperiosteal injections of TGF-beta1 and/or IGF-1 percutaneously. After 1, 3, 5, or 7 days, the rabbits were sacrificed and cambium cellularity or in vitro cartilage forming capacity was determined.
RESULTS:
A significant increase in cambium cellularity and thickness, and in vitro cartilage formation was observed after injection of TGF-beta1 alone or in combination with IGF-1. In 12 month-old rabbits, mean cambium cellularity increased 5-fold from 49 to 237 cells/mm and in vitro cartilage production increased 12-fold from 0.8 to 9.7 mg 7 days after TGF-beta1 (200 ng) injection compared to vehicle controls (P<0.0001). A correlation was observed between cambium cellularity and in vitro cartilage production (R2=0.98). An added benefit of IGF-1 plus TGF-beta1 on in vitro cartilage production compared to TGF-beta1 alone was observed in the 2 year-old rabbits. IGF-1 alone generally had no effect on either cambium cellularity or in vitro cartilage production in any of the age groups.
CONCLUSIONS:
These results clearly demonstrate that it is possible to increase cambium cellularity and in vitro cartilage production in aged rabbit periosteum, to levels comparable to younger rabbits, using local injection of TGF-beta1 alone or in combination with IGF-1, thereby rejuvenating aged periosteum.
PMID: 19064326 [PubMed – indexed for MEDLINE]
For the 2nd study from PubMed “Brief exposure to high-dose transforming growth factor-beta1 enhances periosteal chondrogenesis in vitro: a preliminary report.”
J Bone Joint Surg Am. 2002 May;84-A(5):793-9.
Brief exposure to high-dose transforming growth factor-beta1 enhances periosteal chondrogenesis in vitro: a preliminary report.
Miura Y, Parvizi J, Fitzsimmons JS, O’Driscoll SW.
Source
The Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA.
Abstract
BACKGROUND:
Articular cartilage has limited potential for repair. There have been various attempts aimed at improving the repair process in articular cartilage. Transforming growth factor-beta1 (TGF-beta1) has a stimulatory effect on chondrogenesis in periosteal explants. The purpose of the present study was to determine the effect of brief exposures (i.e., thirty and sixty minutes) of high concentrations of TGF-beta1 on periosteal chondrogenesis.
METHODS:
Five hundred and seventy-three periosteal explants were harvested from forty-six two-month-old male New Zealand White rabbits. Explants were exposed to 50 or 100 ng/mL of TGF-beta1 for thirty or sixty minutes. The amount of cartilage formed was then determined with use of a standardized six-week agarose culture assay.
RESULTS:
There was a significant increase in the amount of cartilage formation (p < 0.01), Type-II collagen content (p < 0.05), and sulfate incorporation (p < 0.0001) in explants treated with TGF-beta1. Maximal stimulation occurred following exposure to 100 ng/mL of TGF-beta1 for thirty minutes. There was also an increase in chondrocyte proliferation as measured by [ (3) H-] thymidine incorporation on day 5 of culture (p < 0.049). Conclusions: The findings of this study indicate that exposure to TGF-beta1 has a stimulatory effect on periosteal chondrogenesis. This stimulatory effect is observed even with a very brief exposure time of thirty minutes. Clinical Relevance: A possible clinical application of these findings is exposure of periosteal grafts that are currently utilized clinically to resurface articular defects to TGF-beta1 during the short time between graft procurement and implantation into the joint. This may obviate the need for intra-articular administration of TGF-beta1 and may enhance the ultimate graft incorporation and quality of cartilage repair.
- PMID: 12004023 [PubMed – indexed for MEDLINE]
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