From the previous post where a patent was being reviewed, one very interesting compound I found which seems to be able to inhibit the endochondral ossifciation process where the cartilage and chondrocytes are ossified into bone, seems to have some potential. From the PubMed study below, the researchers conclude that…
“Our findings indicate that the antiangiogenic factor chondromodulin 1 stabilizes the chondrocyte phenotype by supporting chondrogenesis but inhibiting chondrocyte hypertrophy and endochondral ossification.”
From PubMed study 2 below…
“Cartilage-generated matrix components chondromodulin-I (ChM-I) synergistically stimulates growth and differentiation of chondrocytes in the presence or absence of FGF-2. In contrast, ChM-I inhibits the proliferation of vascular endothelial cells and tube formation, thereby further stimulating cartilage growth and inhibiting replacing cartilage by bone in an early stage. Another cartilage-derived chondromodulin-II (ChM-II) also stimulates cartilage growth. However, ChM-II does not inhibit vascularization but stimulates osteoclast differentiation.”
From source, Chondromodulin, an endogenous anti-angiogenic factor expressed in cartilage, has been suggested to inhibit invasion of endothelial cells into cartilage. In addition, the ectopic administration of ChM1 has been reported to suppress tumorigenesis in vivo. From source, In TMJ (temporomandibular joint), ChM-1 was expressed in the proliferative and hypertrophic zone of condylar cartilage and chondrocyte-like cells in the disc. No expression of ChM-1 was observed in osteoblasts and subchondral bone. ChM-1 may play a role in the regulation of TMJ remodeling by preventing blood vessel invasion of the cartilage, thereby maintaining condylar cartilage and disc integrity.
It can be proposed that chondromodulin may actually have the exact opposite effect in causing height decrease since it is anti-angiogenic. human height can only increased if there is a stable hard bone structure to support the additional bone layered to allow for bone lengthening but maybe chondromodulin can be used instead to hold off the growth plates from completely ossifying and be kept in cartilage form long enough to get other types of bone modulators inside to cause mesenchymal differentiation, chondrocyte proliferation and hypertrophy, and growth factor expression in the cartilage.
From PubMed study link HERE…
Arthritis Rheum. 2011 Sep;63(9):2721-31. doi: 10.1002/art.30335.
Chondromodulin 1 stabilizes the chondrocyte phenotype and inhibits endochondral ossification of porcine cartilage repair tissue.
Klinger P, Surmann-Schmitt C, Brem M, Swoboda B, Distler JH, Carl HD, von der Mark K, Hennig FF, Gelse K.
Department of Orthopaedic Trauma Surgery, University Erlangen-Nuremberg and University Hospital Erlangen, Erlangen, Germany.
To investigate the effect of chondromodulin 1 on the phenotype of osteochondral progenitor cells in cartilage repair tissue.
Self-complementary adeno-associated virus (AAV) vectors carrying chondromodulin 1 complementary DNA (AAV-Chm-1) were applied to cartilage lesions in the knee joints of miniature pigs that were treated by the microfracture technique. Alternatively, isolated porcine osteochondral progenitor cells were infected with AAV-Chm-1 or with AAV-GFP control vectors ex vivo prior to being transplanted into cartilage lesions in which the subchondral bone plate was left intact. The quality of the repair tissue and the degree of endochondral ossification were assessed by histochemical and immunohistochemical methods. The effects of chondromodulin 1 overexpression were also analyzed by angiogenesis assays and quantitative reverse transcriptase-polymerase chain reaction.
AAV-Chm-1-infected cells efficiently produced chondromodulin 1, which had strong antiangiogenic effects, as verified by the inhibition of tube formation of endothelial cells. Gene expression analyses in vitro revealed the cell cycle inhibitor p21WAF1/Cip1 as one target up-regulated by AAV-Chm-1. Direct application of AAV-Chm-1 vectors into microfractured porcine cartilage lesions stimulated chondrogenic differentiation of ingrowing progenitor cells, but significantly inhibited terminal chondrocyte hypertrophy, the invasion of vessel structures, and excessive endochondral ossification, which were otherwise observed in untreated lesions. Indirect gene transfer, with infection of porcine osteochondral progenitor cells by AAV-Chm-1 ex vivo, also supported chondrogenic differentiation of these transplanted cells. AAV-Chm-1-infected cells maintained a chondrocyte-like phenotype and formed a hyaline-like matrix that was superior to that formed by uninfected or AAV-GFP-infected cells.
Our findings indicate that the antiangiogenic factor chondromodulin 1 stabilizes the chondrocyte phenotype by supporting chondrogenesis but inhibiting chondrocyte hypertrophy and endochondral ossification.
Copyright © 2011 by the American College of Rheumatology.
What makes the permanent articular cartilage permanent? [Arthritis Rheum. 2011]
PMID: 21391200 [PubMed – indexed for MEDLINE] Free full text
From PubMed study 2 link HERE…Connect Tissue Res. 1996;35(1-4):303-7.
Roles of cartilage matrix proteins, chondromodulin-I and -II, in endochondral bone formation: a review.
Department of Biochemistry, Faculty of Dentistry, Osaka University, Japan. email@example.com
Insulin induces early chondrogenesis in cultures of a clonal cell-line, ATDC5, which was derived from mouse embryonal carcinoma line AT805. Cartilage-generated matrix components chondromodulin-I (ChM-I) synergistically stimulates growth and differentiation of chondrocytes in the presence or absence of FGF-2. In contrast, ChM-I inhibits the proliferation of vascular endothelial cells and tube formation, thereby further stimulating cartilage growth and inhibiting replacing cartilage by bone in an early stage. Another cartilage-derived chondromodulin-II (ChM-II) also stimulates cartilage growth. However, ChM-II does not inhibit vascularization but stimulates osteoclast differentiation. Therefore, endochondral bone formation is regulated sequentially by cartilage-derived multiple autocrine factors. This opens a new mechanism of regulation of endochondral bone formation.
PMID: 9084668 [PubMed – indexed for MEDLINE]