Prostacyclin is available by prescription in brands such as Flolan.

Prostacyclin regulates bone growth via the Epac/Rap1 pathway.

“Growth plate cartilage is distinct from articular cartilage with respect to COX-2 mRNA expression: whereas articular chondrocytes express very little COX-2, COX-2 expression is high in growth plate chondrocytes, and is increased by Insulin-like Growth Factor-I (IGF-I). In bovine primary growth plate chondrocytes, ATDC5 cells and human metatarsal explants, inhibition of COX activity with non-steroidal anti-inflammatory drugs (NSAIDs) inhibits chondrocyte proliferation and ERK activation by IGF-I. This inhibition is reversed by PGE2 and PGI2, but not by PGD2 or TXB2. Inhibition of COX activity in young mice by intra-peritoneal injections of NSAIDs causes dwarfism. In growth plate chondrocytes, inhibition of proliferation and ERK activation by NSAIDs is reversed by forskolin, 8-Br-cAMP and a prostacyclin analog, iloprost. The inhibition of proliferation and ERK activation by celecoxib is also reversed by 8CPT-2Me-cAMP, an activator of Epac, implicating the small G protein Rap1 in the pathway activated by iloprost. Prostacyclin is required for proper growth plate development and bone growth.”

“Within the growth plate, chondrocytes resting within the reserve zone are recruited to the proliferative zone, wherein IGF-I stimulates cell division, which occurs along the long axis of the bone.”<-Can this recruitment be mimiced in adults to cause new growth plate formation?

“Terminally differentiated cells are found in the hypertrophic zone, wherein glycogen accumulation leads to dramatic cell hypertrophy.”

“IGF-I changes the ratio of activities of the mitogen activated protein (MAP) kinases, ERK1/2 and
p38; relatively high ERK1/2 activity drives proliferation, whereas relatively high p38 activity favors differentiation. The kinase cascades in which ERK1/2 and p38 participate presumably have indirect transcriptional effects, but little is known about the downstream transcriptional
targets of IGF-I in these cells.”

“chondrocytes treated with IGF-I that the growth factor significantly increases the expression of COX-2 in primary bovine growth plate chondrocytes. COX-1 and COX-2 catalyze the same rate-limiting step in the synthesis of prostaglandins, the conversion of arachidonic acid to prostaglandin H2 (PGH2). PGH2 is further metabolized by specific isomerases to produce a
variety of prostanoids, such as prostaglandins, prostacyclins and thromboxanes. COX-1 is constitutively expressed in almost all tissues. COX-2 is normally undetectable in most tissues, but its expression is rapidly induced by injury and proinflammatory factors, and in some tissues mitogens increase COX-2 expression”

“Growth plate chondrocytes release PGE2, which enhances their proliferation”

“whereas COX-2 expression is low in articular chondrocytes, the growth plate expresses
high levels of COX-2 mRNA, and IGF-I increases COX-2 expression and activity in these cells; the ability of IGF-I to stimulate chondrocyte proliferation andERKactivation is dependent on the presence of PGE2 or PGI2; PGI2 is more potent than PGE2 in supporting proliferation and ERK
activation; and PGI2 signals via cAMP activation of the Epac/Rap1 pathway.”

“ibuprofen and celecoxib blocked IGF-I-stimulated proliferation in both primary chondrocytes and in ATDC5 cells at concentrations near or above the IC50 for COX-2 (eg, 50 M ibuprofen, or 2 M celecoxib for primary chondrocytes).”<-Does ibuprofen stunt growth?

“Both the ibuprofen and celecoxib-treated mice were significantly smaller than the mice that received vehicle only”<-and they specifically used doses comprable to those used in children.

“the effects of the protein kinase A inhibitor H89 in chondrocytes is dose-dependent;
low doses tended to increase IGF-I stimulated proliferation slightly, whereas higher doses (such as 10 M), blocked chondrocyte proliferation”

“COX-2 inhibition negatively affects growth plate development in mice by blocking the ability
of IGF-I to activate ERK1/2 and stimulate chondrocyte proliferation; that PGI2 (and to a lesser extent PGE2) and their analogs are able to reverse this blockade suggests that the ability of NSAIDs to suppress chondrocyte proliferation is due to direct inhibition of COX activity. At
least in vitro, we found that the ERK inhibiting effects of celecoxib on chondrocytes are rapidly reversed by a PGI2 analog, suggesting that the dwarfism in mice treated with NSAIDs is due to direct inhibition of COX activity.”