Ghrelin uses the GHS-R1a/Gi/cAMP pathway and induces differentiation only in mature osteoblasts. This ghrelin pathway is impaired in AIS patients

Abstract

We have examined the Acylated Ghrelin (AG)/Gi pathway in different human osteoblastic cell lines. We have found that: 1) AG induces differentiation/mineralization only in mature osteoblasts; 2) the expression of GHS-R1a increases up to the mature cell stage, 3) the action is mediated via the GHS-R/Gi/cAMP pathway only in mature osteoblasts, and 4) osteoblastic cells from adolescent idiopathic scoliosis (AIS) are resistant to the AG/Gi/cAMP pathway. Altogether, these results suggested that AG uses the GHS-R1a/Gi/cAMP pathway to induce differentiation in mature osteoblasts only. This pathway is impaired in AIS osteoblasts. Understanding AG-specific pathways involved in normal and pathological osteoblasts may be useful for developing new treatments for pathologies such as AIS or osteoporosis.

Ghrelin hormone might have a potential role in amelogenesis

“…2,[25][26][27]33,38,39 Multifunctional hormone Ghrelin directly regulates bone development in relation to these proteins. 22,[28][29][30][40][41][42] Odontogenesis occurs as a result of sequential and reciprocal interactions between the oral ectoderm and the neural crest-derived mesenchyme. Tooth crown development morphologically starts with the thickening of the epithelium and progresses through bud, cap and bell forms creating by this thickened epithelium.…”

“…It is noteworthy to point out here; interestingly, Ghrelin enhances the expression of osteoblastic genes in the bone while reducing vascular calcification despite both tissues developing through the same mechanisms. 22,23,[28][29][30][31][32][40][41][42][55][56][57][58][59][60] It has been reported that osteoblastic differentiation and calcification of vascular smooth muscle cells are inhibited by administering high doses of Ghrelin but not at low Ghrelin levels. 30 On the contrary, Maccarinelli et al 32 reported that although…”

“…Besides, stimulating or inhibitory effects on cell proliferation have been reported for these peptides. 28,30,32,60,61 Based on these situations, it was suggested that Ghrelin might create the physiological response in only certain ranges, and when the given dose is exceeded, a resistance mechanism has evolved to Ghrelin. 32 In bone development, Ghrelin stimulates GH release from the pituitary by signaling through the growth hormone secretagogue receptor (GHS-R).…”

“…The formation of dental hard tissues, namely enamel, dentin and cement, is substantially similar to bone development in several ways, including expressing proteins such as GH, IGF‐1, OC and BALP 2,25‐27,33,38,39 . Multifunctional hormone Ghrelin directly regulates bone development in relation to these proteins 22,28‐30,40‐42 …”

“…2 , 25-27 Ghrelin is involved in bone mineralisation and vascular calcification as a regulator by influencing the GH/Insulin-like growth factor-1(IGF-1) axis, bone alkaline phosphatase (BALP), osteocalcin (OC), runt-related transcription factor 2 (Runx2), bone morphogenetic protein-2 (BMP-2) and extracellular signal-regulated kinase (ERK) signalling pathway. 22,[28][29][30][31][32] These factors are known to play a role in the development of the dental hard tissues. 5,6,25,27,33,34 It may be assumed that possible deviations in Ghrelin hormone levels could be attributed to the consequences mentioned above.…”