Monday, May 7, 2012

Thombrospondin 3 can help increase height?

THBS3 is upregulated by LSJL.  As well as 2 and 4. And it's a gene involved in height growth, thus it is important to know it's effects to study the effects of LSJL on height growth.

Skeletal abnormalities in mice lacking extracellular matrix proteins, thrombospondin-1,thrombospondin-3, thrombospondin-5, and type IX collagen.

"Thrombospondin-5 (TSP5) is a large extracellular matrix glycoprotein found in musculoskeletal tissues. TSP5 mutations cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia; both show a characteristic growth plate phenotype with retention of TSP5, type IX collagen (Col9), and matrillin-3 in the rough endoplasmic reticulum{Col9(a1&a3) and MATN3 are both upregulated by LSJL}. TSP5 knockout mice have no obvious skeletal abnormalities, suggesting that TSP5 is not essential in the growth plate and/or that other TSPs may compensate. Col9 knockout mice have diminished matrillin-3 levels in the extracellular matrix and early-onset osteoarthritis. To define the roles of TSP1, TSP3, TSP5, and Col9 in the growth plate, all knockout and combinatorial strains were analyzed. While significant alterations in growth plate organization were found in certain single knockout mouse strains, skeletal growth was only mildly disturbed. dramatic changes in growth plate organization in TSP3/5/Col9 knockout mice resulted in a 20% reduction in limb length, corresponding to similar short stature in humans. type IX collagen may regulate growth plate width; TSP3, TSP5, and Col9 appear to contribute to growth plate organization; and TSP1 may help define the timing of growth plate closure when other extracellular proteins are absent."

"TSP1 and TSP3 are present in the growth plate and may play similar and/or redundant roles with TSP5 in ECM."

"TSP3 knockout mice show accelerated endochondrial ossification and increased trabecular bone in the femoral head"<-TSP3 may slow down endochondral ossification.

"TSP3, TSP5, and type IX collagen play a role in the chondrocyte organization in the growth plate."<-Perhaps then TSP3 may help form new growth plates?

"Loss of type IX collagen resulted in a 5% reduction in limb length. An 8% reduction was observed with loss of both TSP3/5."<-So TSP3 may contribute up to an 8% increase in limb length.

The upregulating of TSP3 may also indicate the organization of new growth plates by LSJL.  TSP3 was highly upregulated by LSJL almost four fold.

According to The interaction of Thrombospondins with extracellular matrix proteins,  TSP-3 is expressed in early proliferative and hypertrophic cartilage.  TSP-3 binds heparin.
Mice with a disruption of the thrombospondin 3 gene differ in geometric and biomechanical properties of bone and have accelerated development of the femoral head.

"Thrombospondin 3 (TSP3) is structurally similar to cartilage oligomeric matrix protein (COMP/TSP5)"

"the trabecular bone proximal to the femoral head growth plate developed at an earlier time in TSP3-null mice than in wild-type mice. Vascular invasion and ossification start in the femoral heads of TSP3-null mice at 9 weeks, whereas the wild-type femoral head is still composed of hypertrophic chondroctyes in a calcified matrix at 15 weeks."

"Thrombospondin 3 (TSP3; encoded by Thbs3) was first discovered during sequencing of DNA upstream from the start of transcription of the mouse Muc1 (episialin) gene. Subsequent studies showed that these two genes are part of a tightly organized, conserved gene cluster on chromosome 3, E3-F1, which also includes glucocerebrosidase (Gba) and metaxin 1 (mtx1)."

"TSP3 is expressed by both osteoblasts and chondrocytes"

"retinoic acid and vitamin D3 can bind to the axial pore in TSP5."  Type 9 collagen interacts with the C-terminus of TSP5.

"[No] phenotypic alterations [were observed] in COMP/TSP5-deficient mice, despite the prevalence of COMP in growth cartilage "

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