Loading effects on bones and possible transdifferentiatiion

Since chondrocytes are what make up growth plates and growth plates are what make you taller.  This is huge.

Molecular events caused by mechanical stress in bone.

“The shape of bone changes as a result of bone remodeling corresponding to physical circumstances such as mechanical stress. The tissue which receives the loaded mechanical stress most efficiently is bone matrix. Recent studies revealed the function of osteocytes as mechanosensors in the early stage of bone remodeling. Loaded mechanical stress is converted to a series of biochemical reactions, and finally activates osteoclasts and osteoblasts to cause bone resorption and formation. Biochemical and molecular biological studies have recently resulted in the identification of the gene of which expression level is changed by mechanical stress. Nitric oxide (NO) and cAMP is secreted in response to mechanical stress in the immediate early stage. Genes encoding enzymes such as glutamate/aspartate transporter (GLAST), nitric oxide synthetase (NOS) and prostaglandin G/H synthetase (PGHS-2) are identified as mechanical stress-responsive. The expression level of IGF-I is enhanced under the control of PTH/PTHrP. The expression of c-fos is increased by loading of mechanical stress[LSJL upregulates C-Fos]. AP1, a heterodimer of c-FOS/c-JUN, functions as a transcription factor of downstream gene(s). Elements including AP1 sites, cyclic AMP response elements (CRE) and shear stress response elements (SSRE) are found in the promoter region of mechanical stress-response genes. The enhanced expression of osteopontin (OPN) in the osteocytes of bone resorption sites was demonstrated by in situ hybridization and immunohistochemistry and transdifferentiation of chondrocytes with the abundant expression of BMP-2 and -4 in the process of distraction osteogenesis was observed.”

“Mechanical stress loaded to bone causes the deformation of bone matrix and generates strain force, which is thought to initiate the mechanotransduction pathway. Since the bone contains a water solution, the strain causes fluid flow in the bone matrix. These represent secondary changes known as streaming potential and shear stress. The activities of ion channels, focal adhesion kinases, as well as the structure of the cytoskeleton of the bone cells, are also modulated by mechanical stress.”<-Wish LSJL we hope that this fluid flow induces differentiation of stem cells into chondrocytes.

“GLAST mRNA expression level in the osteocytes decreased in the loaded ulnae after 6 h of load on two occasions 24 h apart.”

“OPN can inhibit the formation of hydroxyapatite. Immunohistochemical studies demonstrated that OPN was localized only on the surface of matured bone. In contrast, much abundant and broad distribution of OPN was observed in embryonic bone, osteoid and fractured callus”<-OPN is upregulated in LSJL.

“OPN can promote the attachment of osteoclasts possibly via interaction of GRGDS amino acid sequence of OPN and the αvβ3 integrin of the osteoclasts ”

“OPN mRNA was detected predominantly in osteoclasts and osteocytes in the resorption site of the septum.”<-This could suggest that LSJL degrades existing bone to make room for growth plates.

“After 7 days of osteoectomy in the femur of an 11-week-old rat, 0.25 mm of distraction was carried out every 12 h for 28 days. Cartilaginous external callus with endochondral ossification, and endosteal callus formation with membranous ossification were observed at the osteoectomized site. In addition to these typical ossification patterns, we observed the direct bone formation by chondrocyte-like cells with the temporal appearance of fibrous tissue“<-So cells differentiated into chondrocytes with fibrous tissues as an intermediary giving evidence of transdifferentiation.

“The molecular/histological analysis in the process of transchondroid bone formation demonstrated the expression of type II collagen mRNA in the chondrocyte-like cells at the early stage of osteogenesis. With the decrease of type II collagen mRNA, the expression level of type I collagen became enhanced at later stages.”

“the cells present in the transitional region from cartilage to fibrous tissue express alkaline phosphatase mRNA, OPN mRNA and osteocalcin mRNA simultaneously. These results suggest that the differentiation of chondrocyte to hypertrophic chondrocyte is blocked by distraction force, and indicated that chondrocyte may transdifferentiate to the osteoblastic lineage.”

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