Chondromodulin- I With FGF-2 In a Aragose Culture Causes Growth Plate Chondrocyte To Multiply Into Colonies, An Alternative Growth Factor Combination

One of the things that I have been trying to figure out is what would be the best concoction in terms of growth factor formulation that would be needed to be used to cause not just the initial formation of chondrocytes from the differentiation of the the progenitor cells, but also to make sure that the cells can multiply (ie. proliferate) to a high enough rate that can cause the chondrocytes to not just exist alone or in small clumps in the bone matrix, but to actually get the cells to multiply until they form a colony.

I have always felt that if we choose to take the route of a more non-invasive approach to height increase and not go the way of either a complete or partial growth plate transplant, we would have to still start with something. It is only through chondrocyte formation into a colony, leading to proteoglycan and collagen Type II formation which would lead to a completely new generated epiphyseal plate from scratch, so it is critical that we get the correct mixture and sequence of growth factors added to be correct.

I’ve been proposing through previous posts with suggested ideas using different ideas on the sequencing and how to mix the growth factors together to give the optimal, best chance to get the chondrocytes to come into being, and then multiply as much as possible. The last problem would then be to get the individual chondrocytes to stack in columns, which would be absolutely critical for real longitudinal growth.  However, right now I am just trying to figure out possible growth factor combinations and permutations as well as get the sequencing correct.

We have looked at using the PTHrP/PTH with iHH combination to get the growth plates to reverse in the ordinary differentiation direction, as well as try out ideas with TGF-Beta 1, 2, and 3, along with different types of BMPs to see how they would work.

For this post I would propose another growth factor combination, this time with two previous studied growth factors which I felt has some of the best chances of causing chondrocyte proliferation at a high level, FGF-2 and Chondromodulin-I.

From PubMed study “Identification of an autocrine chondrocyte colony-stimulating factor: chondromodulin-I stimulates the colony formation of growth plate chondrocytes in agarose culture.” (Note: the full article was not available)

Biochem Biophys Res Commun. 1997 Dec 18;241(2):395-400.

Identification of an autocrine chondrocyte colony-stimulating factor: chondromodulin-I stimulates the colony formation of growth plate chondrocytes in agarose culture.

Inoue H, Kondo J, Koike T, Shukunami C, Hiraki Y.

Source

Department of Biochemistry, Osaka University Faculty of Dentistry, Japan.

Abstract

Chondrocytes are unique among non-transformed cells in that they are capable of anchorage-independent growth in soft agar. Fibroblast growth factor (FGF) is known as a potent colony-stimulating factor for chondrocytes. However, cartilage extracts contain a potent colony-stimulating activity which is not explicable only by contaminating FGF. We previously isolated the 25 kDa cartilage-specific glycoprotein chondromodulin-I (ChM-I) which stimulates the growth of chondrocytes. In the present study, we observed that ChM-I stimulates the colony formation of rabbit growth plate chondrocytes in agarose culture. ChM-I alone weakly stimulated the formation of chondrocyte colonies, but it markedly stimulated colony formation synergistically in the presence of an optimal dose of FGF-2. This effect was dependent on the dose of ChM-I. These results suggest that ChM-I participates in an autocrine signaling mechanism for the anchorage-independent growth of chondrocytes in vitro.

PMID: 9425282  [PubMed – indexed for MEDLINE]

Analysis and Interpretation: We remember that for the cases of Fibroblast Growth Factors (FGFs), it seems that the FGF-2 and FGF-4 seems to help promote chondrocyte proliferation, while FGF-3 inhibits it. My study on the FGF-2 has been minimal but Tyler’s research suggest that FGF-2 is highly effective. However my previous research into Chondromodulin, Type I and Type II, suggest that this anti-angiogenesis growth factor is very useful in halting the perichondrium penetration by the blood vessels which seems to lead to earlier cartilage calcification. In this study, we find that when Chondromodulin- I is used alone, it has only a weak proliferative ability on chondrocytes placed in a aragose culture. Remember that most cultures used for testing chondrocyte proliferation is either in aragose culture or in calf serum cultures. When however the Chondromodulin-I is combined with FGF-2, we find that the cells multiply to such a degree that they cause colony formation, at least in the aragose culture. The implications of these results means that we should try to put the combination of Chondromodulin-I added with FGF-2 as a good possible combination for minimal invasive height increase methods for at least one step in the sequence of injection method, if we even choose to go with a injection sequence method.

 

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