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

Ronan Barre; Nicolas Beton; Aurélie Batut; Frank Accabled; Jerome Sales de Gauzy; Françoise Auriol; Sanaa Eddiry; Maithe Tauber; Sara Laurencin; Jean Pierre Salles; Isabelle Gennero

doi:10.1016/j.bbrep.2020.100782

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

Biochem Biophys Rep. 2020 Sep 11:24:100782. doi: 10.1016/j.bbrep.2020.100782. eCollection 2020 Dec.

Authors

Ronan Barre^{1

2}, Nicolas Beton^{2

3}, Aurélie Batut^{2

3}, Frank Accabled^{3

4}, Jerome Sales de Gauzy^{3

4}, Françoise Auriol^{2

5}, Sanaa Eddiry^{2

5}, Maithe Tauber^{2

3

5}, Sara Laurencin^{2

6}, Jean Pierre Salles^{2

3

5}, Isabelle Gennero^{2

3

7}

Affiliations

¹ Oral Biology Department, Faculty of Odontology, Paul Sabatier Toulouse III University, France.
² INSERM, UMR1043, Centre de Physiopathologie de Toulouse Purpan, CHU Toulouse, France.
³ Faculty of Medicine, Paul Sabatier Toulouse III University, France.
⁴ Orthopedic Department, Children Hospital, CHU Toulouse, France.
⁵ Endocrinology and Bone Pathologies Department, Children Hospital, CHU Toulouse, France.
⁶ Periodontology Department, Faculty of Odontology, Paul Sabatier Toulouse III University, France.
⁷ Clinical Biochemistry Department, Federative Institute of Biology, CHU Toulouse, France.

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.

Keywords: Acylated ghrelin; Adolescent idiopathic scoliosis; Differentiation; GHRS1a; Osteoblast; cAMP.