Osteocytes orchestrate browning: emerging signals in bone-fat crosstalk: a systematic review.

Abstract

<h4>Background</h4>Bone is increasingly viewed as an active component of systemic physiology rather than a solely structural tissue. Among its resident cells, osteocytes have emerged as important endocrine regulators capable of influencing metabolic processes in distant organs. Several osteocyte-derived factors have been linked to pathways that govern energy balance. Recent work suggests that these signals may also affect the browning of white adipose tissue, a thermogenic remodeling process.<h4>Scope of review</h4>This systematic review specifically examines the evidence supporting the regulatory role of osteocytes in adipocyte browning. The experimental studies investigated how osteocyte-related signals-such as sclerostin suppression, PPARγ deletion, Sirt1 activation, or downstream BMP modulation-affect thermogenic gene expression, and beige adipocyte differentiation across peripheral and marrow fat depots. Despite heterogeneity in design and endpoints, the collectively available evidence indicates that osteocytes can influence the induction or repression of adipocyte browning programs.<h4>Major conclusion</h4>Current evidence supports a role for osteocytes as modulators of adipocyte browning, integrating skeletal signaling with systemic metabolic responses. However, the findings remain preliminary due to limited osteocyte-specific targeting, depot-specific variability, and contextual differences across models. Establishing the physiological relevance of osteocyte-derived signals and defining the conditions under which they influence adipose plasticity will be essential for advancing therapeutic exploration. Understanding this bone-fat crosstalk may ultimately provide new opportunities to address metabolic and skeletal disorders through shared regulatory pathways.