Role and molecular mechanism of ghrelin in degenerative musculoskeletal disorders

Abstract

Ghrelin is a brain-gut peptide, and the first 28-peptide that was found in the gastric mucosa. It has a growth hormone (GH)-releasing hormone-like effect and can potently promote the release of GH from pituitary GH cells; however, it is unable to stimulate GH synthesis. Therefore, ghrelin is believed to play a role in promoting bone growth and development. The correlation between ghrelin and some degenerative diseases of the musculoskeletal system has been reported recently, and ghrelin may be one of the factors influencing degenerative pathologies, such as osteoporosis, osteoarthritis, sarcopenia and intervertebral disc degeneration. With population ageing, the risk of health problems caused by degenerative diseases of the musculoskeletal system gradually increases. In this article, the roles of ghrelin in musculoskeletal disorders are summarized to reveal the potential effects of ghrelin as a key target in the treatment of related bone and muscle diseases and the need for further research.

Keywords: ageing; ghrelin; intervertebral disc degeneration; osteoarthritis; osteoporosis; sarcopenia.

FIGURE 1

Ghrelin is correlated with the progression of multiple degenerative musculoskeletal disorders including OP, OA sarcopenia and IVDD. (A) Signal pathway: MAPK/PI3K, GHSR/ERK and GHSR/PI3K/AKT. (B) Signal pathway: JAK2/STAT3/IRF‐1, NF‐kB and AKT. (C) Signal pathway: p38/C/EBPβ, PI3Kβ, mTORC2 and p38. (D) Signal pathway: NF‐κB and AKT. AKT, protein kinase B; ERK, extracellular regulated protein kinase; GHSR, growth hormone secretagogue receptor; IVDD, intervertebral disc degeneration; MAPK, mitogen‐activated protein kinase; mTORC2, mammalian target of rapamycin complex 2; OA, osteoarthritis; OP, osteoporosis; PI3K, phosphoinositide 3‐kinase; PI3Kβ, phosphoinositide 3‐Kinase β.