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An MCH neuroendocrine circuit in lateral hypothalamus for bone mass regulation

ABSTRACT: Neuroendocrine regulation is essential for maintaining metabolic homeostasis. However, whether neuroendocrine pathway influence bone metabolism is unelucidated. Here, we identify a central neuroendocrine circuit that directly controls osteogenesis. Using virus based tracing, weidentify that melanin concentrating hormone (MCH) expressing neuronsin the lateral hypothalamus (LH) are connected to the bone.Chemogenetic activation of MCH neurons in the LH induces osteogenesis, whereas inhibiting these neurons reduces osteogenesis.Meanwhile, MCH is released into the circulation upon chemogenetic activation of these neurons. Single cell sequencing reveals that blocking MCH neurons in the LH diminishes osteogenic differentiation of bone marrow stromal cells (BMSCs). Mechanistically, MCH promotes BMSC differentiation by activating MCHR1 via PKA signaling and activating MCHR1 by MCH agonists attenuate osteoporosis in mice. By elucidating a brain-bone connection that autonomously enhances osteogenesis, these findings uncover the neuroendocrinological mechanisms governing bone mass regulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE239973 | GEO | 2025/08/01

REPOSITORIES: GEO

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