Does LSJL only increase intermedullary pressure or does it have extra anabolic effects? The next few studies address what happens only if intermedullary pressure is increased. It’s possible that LSJL’s effects are due solely to an increase in vascularization which makes it less promising for adult height growth although it would still be possible to induce adult height growth. These studies are performed on rats much older than those used in LSJL but no impact on longitudinal bone growth was studied. However, it still shows even in aged individuals developmental genes like BMP-2 and TGF-Beta can be stimulated.
Dynamic hydraulic fluid stimulation regulated intramedullary pressure
“Physical signals within the bone, i.e. generated from mechanical loading, have the potential to initiate skeletal adaptation. Strong evidence has pointed to bone fluid flow (BFF) as a media between an external load and the bone cells, in which altered velocity and pressure can ultimately initiate the mechanotransduction and the remodeling process within the bone. Load-induced BFF can be altered by factors such as intramedullary pressure (ImP) and/or bone matrix strain, mediating bone adaptation. BFF induced by ImP alone, with minimum bone strain, can initiate bone remodeling. To apply ImP as a means for alteration of BFF, it was hypothesized that non-invasive dynamic hydraulic stimulation (DHS) can induce local ImP with minimal bone strain to potentially elicit osteogenic adaptive responses via bone–muscle coupling. The goal of this study was to evaluate the immediate effects on local and distant ImP and strain in response to a range of loading frequencies using DHS. Simultaneous femoral and tibial ImP and bone strain values were measured in three 15-month-old female Sprague Dawley rats during DHS loading on the tibia with frequencies of 1 Hz to 10 Hz. DHS showed noticeable effects on ImP induction in the stimulated tibia in a nonlinear fashion in response to DHS over the range of loading frequencies, where they peaked at 2 Hz. DHS at various loading frequencies generated minimal bone strain in the tibiae. Maximal bone strain measured at all loading frequencies was less than 8 με. No detectable induction of ImP or bone strain was observed in the femur. This study suggested that oscillatory DHS may regulate the local fluid dynamics with minimal mechanical strain in the bone, which serves critically in bone adaptation. These results clearly implied DHS’s potential as an effective, non-invasive intervention for osteopenia and osteoporosis treatments.”
“bone fluid flow (BFF) with altered velocity or pressure acts as a communication media between an external load and the bone cells, which then regulate bone remodeling. In converse, discontinuous BFF can initiate bone turnover and result in osteopenia”
“Induced ImP possibly triggers the transformation of the bone nutrient vasculature, leading to the ultimate alteration in blood supply to the bone.”
“The ImP reached the peak at 2 Hz.” at about 15mmHg.
“Dynamic hydraulic stimulation (DHS) [is] a loading modality to induce anabolic responses in bone. To further study the functional process of DHS regulated bone metabolism, the objective of this study was to evaluate the effects of DHS on cortical bone and its alterations on gene expressions of osteogenic growth factors and transcription factors as a function of time. Using a model system of 5-month-old hindlimb suspended (HLS) female Sprague–Dawley rats, DHS was applied to the right tibiae of the stimulated rats with a loading frequency of 2 Hz with 30 mmHg (p–p) dynamic pressure, 5 days/week, for a total of 28 days. Midshafts of the tibiae were analyzed using μCT and histology. Total RNA was analyzed using RT-PCR on selected osteogenic genes (RUNX2, β-catenin, osteopontin, VEGF, BMP2, IGF-1, and TGF-β) on 3-, 7-, 14- , and 21-day. Results showed increased Cort.Th and Ct.BV/TV as well as a time-dependent fashion of gradual changes in mRNA levels upon DHS. While DHS-driven fold changes of the mRNA levels remained low before Day-7, its fold changes started to elevate by Day-14 and then dropped by Day-21. This study further delineates the underlying molecular mechanism of DHS-derived mechanical signals, and its time-dependent optimization.”
BMP2, IGF-1 and Tgf-Beta are all pro chondrogenic.
“Bone formation progresses over time after the initiation of mechanical loading. Within 24–48 hr after mechanical loading starts, new osteoblasts lay on the bone surface and contribute to bone formation that is observed after 96 hr of loading. Bone formation follows a time-dependent manner, in which it increases between 5 and 12 days of loading and returns back to baseline levels after 6 weeks of loading. These data suggest that the whole cycle of bone formation, including osteoblast recruitment followed by matrix production, lasts for about 5 weeks before declining back to baseline levels”<-new osteoblasts implies cell differentiation which could mean new chondrocytes as well.
Dynamic Hydraulic stimulation increased the periosteal surface.
At seven days interestingly the levels of the pro-chondrogenic genes IGF-1, BMP2, and TGF-Beta were low. At 14 days they were all increased relative to control.
“HS may compress the veins within the skeletal muscle and increase the vasculature pressure gradient that promotes capillary blood flow in bone. Increase of capillary filtration may further increase ImP and induce BFF that ultimately promote bone regeneration”
I think LSJL does more than just pure Hydraulic stimulation does.
“Osteoblasts [orginiate] from MSCs”
“Our group previously presented a longitudinal study of bone marrow MSC quantification under DHS in a rat HLS model, where the MSC number was greatly increased in response to DHS by day 14 and diminished by day 21. MSCs may have completed proliferation and begun to differentiate towards osteoblastogenesis at this stage. In the meantime, the induced mRNA levels of the selected genes that we observed in the present study may couple the process of transforming MSC proliferation and differentiation into osteoblasts, which commit to the subsequent bone formation.”<-so maybe why the pro-chondrogenic genes were low at day 7 is that MSCs were proliferating rather than differentiating into chondrocytes.
