Inflammation to Grow Tall?

We've learned that HMGA2 is a vital gene for height growth.  That Lin28 can increase HMGA2 by inhibiting Let-7.  However, barring a way to directly stimulate Lin28 or Myc, let-7 inhibition mainly occurs through inflammation driven NF-kappaB pathway.  NF-kappaB promotes stemness but it also causes apoptosis usually resulting in no net change in growth.  Although apoptosis may be involved in height growth.  However, in adult growth plates where there is no cartilage in the bone all the apoptosis will occur in bone cells(of course there is cartilage in the knee joint).  The NF-kappaB pathway no encourages an increase in stemness allowing for chondrogenic differentiation.  So you're trading out bone cells for potential chondrogenic cells.

This may mean that you might want to purposefully induce inflammation in the bone with LSJL in bones that do not have cartilage in them.  The NF-kappaB pathway was found to be crucial to induce chondrogenesis but you still may want to inhibit other inflammatory cytokines like IL-1 and TNF-alpha.  Shear strain(LSJL induces shear strain) has been found to induce IL-6 in chondrocytes, although we don't know if this will occur in bone or stem cells.

Obesity may induce inflammation:

Metabolomic profiling reveals mitochondrial-derived lipid biomarkers that drive obesity-associated inflammation.

"[We] compare traditional lard-based high fat diets (HFD) to "Cafeteria diets" (CAF) consisting of nutrient poor human junk food. [There's a] rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. We profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Clusters of fatty acids and acylcarnitines [were elevated]. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. [There were] strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations."

So high fat and saturated fat diets may increase inflammation.

"Lauroyl carnitine can activate NFΚB signaling"  Here's L-Carnitine: I'm not sure how it compares to Lauroyl L-carnitine NOW Foods L- Carnitine Tartrate 1000mg, 100 Tablets.

Here's a study showing how heterotopic ossification is modified by inflammation, we don't want heterotopic ossification we want chondrogenesis within the bone(endochondral ossification) but if heterotopic ossification can occur so too should endochondral ossification:

Heterotopic Ossification Following Burn Injury: The Role of Stem Cells.

"Heterotopic ossification (HO) [is] the abnormal development of bone tissue in soft-tissue locations. HO is highly associated with burn injury{can we mimic some of the molecules induced by bone injury within the bone?}."

"a 60% incidence [of heterotopic ossification] is observed in patients with severe burns."<-so induce the same factors caused by severe burns in the bone marrow?

"One example of a primary cause of HO is the genetic disorder fibrodysplasia ossificans progressiva (FOP), in which ectopic ossification progresses episodically and in response to minor trauma beginning in childhood"<-We need to study this disorder because it does induce endochondral ossification.  Keep inducing mini-growth plates in the bone and you'll grow tall forever.

"HO lesions from subjects with FOP were found to stain strongly for endothelial (angiopoietin-1 receptor [TIE-2] and von Willebrand factor) and osteogenic (osteocalcin) markers"

"Endothelial cells transdifferentiate into the mesenchymal stem cells (MSCs) that subsequently form ectopic bone in a process called endothelial-to-mesenchymal transition (EndMT)."<-This is something we don't want to happen.  We want to use the mesenchymal cells already in the bone marrow.

"BMP-2 producing fibroblasts caused both the recruitment of mesenchymal cells and the upregulation of the peroxisome proliferatoractivated receptor  γ pathway. Upregulation of the peroxisome proliferator-activated receptor γ pathway leads to the differentiation of the recruited mesenchymal cells to brown adipocytes. The brown adipocytes then create the hypoxic microenvironment necessary for endochondral ossification to occur by converting nutrients and oxygen into heat through the uncoupling of oxidative phosphorylation."<-So fat in bone can create hypoxic environment for chondrogenic differentiation.

Burn injury involves both hypoxia and inflammation which is likely which it can induce endochondral ossification.  Safer ways to induce these things should be used.

Long-term aerobic exercise reduces inflammation and likely makes cells more resistance to hypoxia.

Here's a study that shows inflammation can be induced by prolonged exercise:

Effect of inflammation induced by prolonged exercise on circulating erythroid progenitors and markers of erythropoiesis.

"Exercise in humans augments the mobilization of circulating hematopoietic progenitor cells (CD34(+)) from the bone marrow. We investigated the effect of inflammation on erythroid marrow activity by mobilization of erythroid progenitor cells (EPs) along with soluble markers of erythropoiesis.

Ten healthy athletes who participated in an ultradistance foot race participated in the study. Peripheral blood mononuclear cells were isolated, before (phase I), at the end (phase II), and at 48 h post-race (phase III). EPs were detected as burst colony forming units (BFU-e) and colonies were scored at day 14. Markers of inflammation (C-reactive protein, serum amyloid-A, interleukin-6, ferritin and S100B) and bone marrow activity (erythropoietin, soluble transferrin receptor and lipocalin-2) were assessed.

An approximately three-fold decrease in BFU-e number was observed at phase II. sTfR concentrations were also decreased at phase II and remained decreased at phase III. However, EPO and lipocalin-2 concentrations reached a maximum value at phase II, with a tendency to decrease at phase III.

Exercise-induced inflammation modulates bone marrow homeostasis leading to an increase in leukocyte turnover and a decrease in erythroid compartment. It appears that lipocalin-2 is the main factor that regulates the production and mobilization of EPs."

IL-6 levels were huge post race but returned to normal after 48 hours.

"The increase in progenitor cells [is] a consequence of mobilization processes occurring in the bone marrow after short supra-maximal exercise, whereas a longer time period leads to a reduction in the amount of cells due to inflammation"

However, there have been no reports of marathon runners growing taller.  Prolonged running should induce both hypoxia and inflammation in the bone marrow.  Running may not induce hydrostatic pressure and there may not be release of TGF-Beta1 to induce chondrogenic differentiation.

Hemopoietic and angiogenetic progenitors in healthy athletes: different responses to endurance and maximal exercise.

"In healthy amateur runners, we collected venous blood before, at the end of, and the day after a marathon race, and before and at the end of a 1.5-km field test, and measured hemopoietic and angiogenetic progenitors, as well as plasma or serum concentrations of several cytokines/growth factors. After the marathon, CD34(+) cells were unchanged, [but] decreased number of colonies for both erythropoietic (BFU-E) and granulocyte-monocyte (CFU-GM) series, returning to baseline the morning post-race. CD34(+) cells[bone marrow derived progenitors], BFU-E, and CFU-GM increased after the field test. Angiogenetic progenitors, assessed as CD34(+)KDR(+) and CD133(+)VE-cadherin(+) cells or as adherent cells in culture expressing endothelial markers, increased after both endurance and maximal exercise but showed a different pattern between protocols. Interleukin-6 increased more after the marathon than after the field test, whereas hepatocyte growth factor and stem cell factor increased similarly in both protocols. Plasma levels of angiopoietin (Ang) 1 and 2 increased after both types of exercise, whereas the Ang-1-to-Ang-2 ratio or vascular endothelial growth factor-A were little affected. Circulating hemopoietic progenitors may be utilized in peripheral tissues during prolonged endurance exercise[so the stem cells are being used up rather than differentiating into chondrocytes to grow taller]. Endothelial progenitor mobilization after exercise in healthy trained subjects appears modulated by the type of exercise. Exercise-induced increase in growth factors suggests a physiological trophic effect of exercise on the bone marrow."

So we're not sure yet how to apply inflammation to grow taller.  Slightly longer durations of LSJL may induce a little inflammation and stimulate the NF-kappaB pathway.

According to Pro-Inflammatory Cytokines Produced by Growth Plate Chondrocytes May Act Locally to Modulate Longitudinal Bone Growth, inflammatory cytokines are produced endogenously by the growth plates and inhibiting these cytokines was shown to increase growth.  "The combined treatment with anakinra plus etanercept (500 + 500 µg/ml) resulted in a growth which was 20.3 ± 1.9% above control bones".  "when metatarsal bones were treated with the combination of anakinra plus etanercept the hypertrophic zone height was significantly increased by 43% and the hypertrophic zone area increased by 69%."  Note those two drugs inhibit IL-1Beta and TNF-alpha without inhibiting IL-6 which is likely why inhibiting those compounds have beneficial effects.  As the body can just use IL-6 for some of the beneficial effects of inflammatory cytokines with less bad effects.