Adipokine Regulation in Bone Metabolism

Adipokines, a class of bioactive proteins secreted predominantly by white adipose tissue and bone marrow adipocytes, have emerged as critical regulators of skeletal remodelling. These factors exert endocrine, paracrine and autocrine effects on osteoblasts, osteoclasts and their mesenchymal progenitors, thereby fine-tuning the balance between bone formation and resorption. Well-characterised adipokines such as leptin and adiponectin display dual actions: leptin modulates osteoblast activity via central and peripheral pathways, whereas adiponectin influences osteogenesis through receptor-mediated signalling cascades. Novel mediators including visfatin, omentin-1, nesfatin-1 and apelin have been implicated in the control of osteoclast differentiation and osteoblast survival, often via pro-inflammatory or anti-inflammatory mechanisms. Intracellular pathways such as Wnt/β-catenin, PI3K/Akt, MAPK and mTOR are recurrently engaged by adipokines to regulate gene expression programmes governing cell proliferation, differentiation and apoptosis. Dysregulation of adipokine networks is associated with obesity-related bone fragility, age-related osteoporosis and inflammatory bone loss, underscoring their translational potential as biomarkers and therapeutic targets. Recent advances reveal intricate cross-talk between adipose and skeletal tissues, positioning adipokines at the crossroads of energy homeostasis and bone health.

Research from Nature Portfolio

Recent studies have shown that adiponectin enhances osteogenic differentiation of bone marrow mesenchymal stem cells by activating the Wnt/β-catenin pathway. Enhanced expression of β-catenin and downstream osteogenic markers in adiponectin-treated cells led to increased bone formation in defect models, emphasising a direct pro-osteogenic role.

Investigations into vaspin, a serine protease inhibitor derived from visceral fat, revealed that it attenuates pre-osteoblastic differentiation by upregulating miR-34c. Vaspin also activates the PI3K/Akt signalling axis, forming a feedback loop with miR-34c to control osteoblast gene expression, thus highlighting a novel mechanism by which adipokines can inhibit bone formation.

Adipokine Regulation in Bone Metabolism publication trend

The graph below shows the total number of articles in adipokine regulation in bone metabolism across all publications each year (not limited to Nature Index journals).

Technical terms

Adipokine: Hormone-like protein produced by adipose tissue that modulates metabolic and inflammatory processes.

Osteoblast: Bone-forming cell responsible for synthesising bone matrix and mineralisation.

Osteoclast: Multinucleated cell specialised in bone resorption during remodelling.

Bone marrow mesenchymal stem cell (BMSC): Multipotent progenitor capable of differentiating into osteoblasts and adipocytes.

RANKL: Receptor activator of nuclear factor κB ligand, key cytokine driving osteoclast differentiation.

Wnt/β-catenin pathway: Signalling cascade that promotes osteoblast proliferation and differentiation.

PI3K/Akt signalling: Intracellular kinase pathway regulating cell growth, survival and differentiation.

References

1. Aging alters the effect of adiponectin receptor signaling on bone marrow‐derived mesenchymal stem cells. Aging Cell (2024).
2. Visfatin Enhances RANKL-Induced Osteoclastogenesis In Vitro: Synergistic Interactions and Its Role as a Mediator in Osteoclast Differentiation and Activation. Biomolecules (2024).
3. The role of adipokines in osteoporosis management: a mini review. Frontiers in Endocrinology (2024).
4. Adiponectin regulates BMSC osteogenic differentiation and osteogenesis through the Wnt/β-catenin pathway. Scientific Reports (2017).
5. Vaspin regulates the osteogenic differentiation of MC3T3-E1 through the PI3K-Akt/miR-34c loop. Scientific Reports (2016).