Grow in Height with Amylin and adrenomedullin?

Systemic administration of amylin increases bone mass, linear growth, and adiposity in adult male mice.

"Amylin is a peptide hormone cosecreted with insulin from the pancreatic beta-cells that can act as an osteoblast mitogen. Adult male mice[age 40-50 days weighing 25 to 32 grams] were given daily subcutaneous injections of amylin (10.5 microgram) or vehicle (n = 20 in each group) for 4 wk. Histomorphometric indices of bone formation increased 30-100% in the amylin-treated group, whereas resorption indices were reduced by approximately 70% (P < 0.005 for all indices). Total bone volume in the proximal tibia was 13.5 +/- 1.4% in control animals and 23.0 +/- 2.0% in those receiving amylin (P = 0.0005). Cortical width, tibial growth plate width[by about double], tibial length[by about 5-10%], body weight, and fat mass were all increased in the amylin-treated group. It is concluded that systemic administration of amylin increases skeletal mass and linear bone growth."

Amylin alters renal calcium handling and increases circulating IGF-1 levels.

"[Chondrocytes] show increased thymidine incorporation and increased cell numbers after treatment for 24 h with amylin in concentrations of 1 × 10−10 M and greater"

Amylin and adrenomedullin: novel regulators of bone growth.

"The peptide hormones amylin and adrenomedullin [are] known to circulate at picomolar concentrations. Adrenomedullin is also produced locally in bone. Amylin and adrenomedullin are related peptides with some homology to both calcitonin and calcitonin gene-related peptide."

"Both amylin and adrenomedullin have also been found to act on chondrocytes, stimulating their proliferation in culture and increasing tibial growth plate thickness when administered systemically to adult mice."

Relationships between fat and bone.

"Fat mass [is associated with] with the secretion of bone active hormones from the pancreatic beta cell (including insulin, amylin, and preptin), and the secretion of bone active hormones (e.g., estrogens and leptin) from the adipocyte."

"Amylin is co-secreted with insulin and potently inhibits bone resorption"

"deletion of GLP-2 receptor leads to marked skeletal deficits in growing mice"

Adrenomedullin(22-52) combats inflammation and prevents systemic bone loss in murine collagen-induced arthritis.

"DBA/1 mice with collagen-induced arthritis (CIA) were treated with 1.2 μg/gm adrenomedullin(22-52) , adrenomedullin, or saline at arthritis onset."

"Tumor necrosis factor α, interleukin-6 (IL-6), and IL-17A levels were significantly decreased in the joints of mice with CIA treated with adrenomedullin or adrenomedullin(22-52) as compared to controls, whereas IL-4 and IL-10 levels were increased. Adrenomedullin(22-52) was more effective than adrenomedullin in modulating cytokine content and enhanced Treg cell function without changing Treg cell expression compared to controls. Adrenomedullin receptor binding and transcriptional adrenomedullin receptor expression were markedly increased in joints from controls, whereas adrenomedullin receptor binding was considerably decreased in treated animals. Mice with CIA treated with adrenomedullin or adrenomedullin(22-52) had considerably fewer apoptotic chondrocytes and diminished cartilage degradation. Adrenomedullin(22-52) completely prevented systemic bone loss by preserving osteoblastic activity, but without changes in osteoclastic activity."

" Murine and human chondrocytes express adrenomedullin receptors"

"Adrenomedullin receptors are composed of the calcitonin-like receptor (CLR). CLR is a 7-transmembrane G protein associated with 1 of 3 single membrane–spanning receptor activity–modifying proteins (RAMPs), namely, RAMP-1, RAMP-2, or RAMP-3."

Expression of adrenomedullin and its receptor by chondrocyte phenotype cells.

"[We] investigate the secretion of adrenomedullin (AM) by chondrocyte phenotype cells and whether or not AM effects this proliferation in a cAMP-dependent fashion. Chondrocyte phenotype cells expressed AM and the AM receptor, and secreted high concentration of AM into the culture medium. When added to cultures, AM increased the intracellular cAMP level and decreased the number of these cells in a similar concentration-dependent fashion. Addition of forskolin and dibutyryl-cAMP caused a significant decrease in the number of these cells. Furthermore, the effect of AM was inhibited by a cAMP-dependent protein kinase A inhibitor (H89). The present findings indicate that AM has an autocrine/paracrine type of anti-proliferative effect on these cells mediated via a cAMP-dependent pathway and raise the possibility that AM plays a role in the local modulation of a process of de-differentiation by culturing"

So Adrenomedullin likely helps further the differentiation of chondrocyte cells.

"When chondrocytes are cultured, there is prompt down-regulation of expression of cartilage-specific genes, including those encoding type-2, -9, and -11 collagens and aggrecan{all up in LSJL}, as well as concomitant initiation or up-regulation of expression of fibroblast-associated genes, including those for type-1{up}, -3{up}, and -5{up} collagens and versican{up}"

"Cyclic AMP acts as a second messenger in various tissues, including fibroblasts and chondrocytes, and in cultured fibroblasts and chondrocytes, cAMP analogs decrease thymidine incorporation into DNA"

"the addition of forskolin and dibutyryl-cAMP caused a significant decrease in cell population. AM activity is likely to be primarily mediated via the cAMP pathway and involves inhibition of the mitogen-activated protein kinase cascade"

"H89, a PKA inhibitor, blocked the effects of AM on chondrocyte phenotype cells"

Effects of amylin and adrenomedullin on the skeleton.

"Amylin is secreted following eating and may direct calcium and protein absorbed from the meal into new bone synthesis. Amylin circulates in high concentrations in obese individuals, and might contribute to the association between bone mass and fat mass. "

"[Amylin is] co-secreted with insulin from the pancreatic B-cell"

"adrenomedullin [is] in maturing cartilage, hypertrophic cartilage and in osteoblasts of the developing bone."

Amylin increases tibial length and growth plate width.