LSJL upregulates Bone sialoprotein.

Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization.

“Bone sialoprotein (BSP) is an anionic phosphoprotein in the extracellular matrix of mineralized tissues, and a promoter of biomineralization and osteoblast development. Previous studies on the Bsp-deficient mouse (Bsp-/-) have demonstrated a significant bone and periodontal tissue phenotype in adulthood.  Early endochondral ossification in the Bsp-/- mouse was studied. Embryonic day 15.5 (E15.5) wild-type (WT) tibiae showed early stages of ossification that were absent in Bsp-/- mice. At E16.5, mineralization had commenced in the Bsp-/- mice, but staining for mineral was less intense and more dispersed compared with that in WT controls. Tibiae from Bsp-/- mice also demonstrated decreased mineralization and shortened length at postnatal day 0.5 (P0.5) compared to WT bones. There was no detectable difference in the number of tartrate-resistant acid phosphatase-positive foci at P0.5, although the P0.5 Bsp-/- tibiae had decreased Vegfα expression compared with WT tissue. Due to the shortened tibiae the growth plates were examined and determined to be of normal overall length. However, the length of the resting zone was increased in P0.5 Bsp-/- tibiae whereas that of the proliferative zone was decreased, with no change in the hypertrophic zone length of Bsp-/- mice{So BSP can possibly aid in the transition of resting zone chondrocytes to proliferative chondrocytes}. A reduction in cells positive for Ki-67, an S-phase cell-cycle marker, was noted in the proliferative zone. Decreased numbers of TUNEL-positive hypertrophic chondrocytes were also apparent in the Bsp-/- tibial growth plates, suggesting decreased apoptosis. Expression of the osteogenic markers Alp1, Col1a1, Sp7, Runx2, and Bglap was reduced in the endochondral bone of the neonatal Bsp-/- compared to WT tibiae. These results suggest that BSP is an important and multifaceted protein that regulates both chondrocyte proliferation and apoptosis as well as transition from cartilage to bone during development of endochondral bone.”

From this information though we can’t be clear whether the loss of BSP slows down growth or results in alteration of adult bone length.

“Overexpression of BSP downstream of a CMV promoter (CMV-BSP) in vivo resulted in mice that are significantly smaller than their wild-type controls. There are also defects in their endochondral bones, with aberrant growth plate formation and development. The growth plates of the CMV-BSP mice have no change in overall length, although there was an increase in hypertrophic zone size and number of hypertrophic chondrocytes. At 8 weeks of age, the mice also show a decrease in the proliferative zone length. This suggests that the overexpression of BSP promotes terminal differentiation in these chondrocytic cells.”<-So mice with overexpression of BSP had shorter bones.  Perhaps lower levels of BSP is beneficial as growth may be slower but take place over a longer period of time.

“these CMV-BSP mice have increased numbers of osteoclasts in their trabecular bone, suggesting that BSP promotes osteoclast formation”

“Mice deficient in BSP (Bsp−/−) also have decreased long bone length and cortical bone thickness relative to wild-type (WT) mice at 4 months of age. Conversely, they have a higher trabecular bone density than WT mice, but an apparent lower rate of bone turnover. This decrease in turnover could be due, in part, to a decrease in osteoclast numbers.”

“lack of BSP results in delayed patterns of bone development, which can be attributed, in part, to the reduction in the proliferation and apoptosis of the chondrocytes within the growth plate.”<-Delayed development not necessarily reduced development.

” The RP fraction was assayed for expression of developmental markers of chondrocyte development Alp1, Col2a1, Acan, Runx2, and Sox9 and no differences were seen between genotypes”