Adiponectin signalling in bone homeostasis, with age and in disease

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Colleges, School and Institutes


Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin resistance. Within the bone, osteoblasts and osteoclasts express the adiponectin receptors, however, there are conflicting reports on the effects of adiponectin on bone formation and turnover. Many studies have shown a pro-osteogenic role for adiponectin in in vivo murine models and in vitro: with increased osteoblast differentiation and activity, alongside lower levels of osteoclastogenesis. However, human studies often demonstrate an inverse relationship between adiponectin concentration and bone activity. Moreover, the presence of multiple isoforms of adiponectin and multiple receptor subtypes has the potential to lead to more complex signalling and functional consequences. As such, we still do not fully understand the importance of the adiponectin signalling pathway in regulating bone homeostasis and repair in health, with age and in disease. In this review, we explore our current understanding of adiponectin bioactivity in the bone; the significance of its different isoforms; and how adiponectin biology is altered in disease. Ultimately, furthering our understanding of adiponectin regulation of bone biology is key to developing pharmacological and non-pharmacological (lifestyle) interventions that target adiponectin signalling to boost bone growth and repair in healthy ageing, following injury or in disease.

The principal cellular constituents of bone (primarily osteoblasts and osteoclasts) rapidly respond to circulating signals, altering global levels of bone formation and resorption respectively, and thus impacting bone homeostasis.1,2,3 The effects of adiponectin in bone have been researched in multiple conditions; however, these studies report variable outcomes with little explanation. Further exploration of adiponectin signalling is essential to fully understand the possibility of promoting or inhibiting its actions during ageing or disease. Of note, very few studies have examined the effect of adiponectin on osteoclasts, so we understand much less about its role in bone turnover. Here we explore the current literature on adiponectin in bone, looking in depth at the comparison between human and murine in vivo and in vitro data in health, with age and in disease, with reference (where possible) to the adiponectin isoform described.


Original languageEnglish
Article number1
JournalBone Research
Publication statusPublished - 7 Jan 2021


  • bone, adiponectin, homeostasis, Osteoporosis