Abstract
Bone has traditionally been regarded as a structural organ that supports and protects the various organs of the body. Recent studies suggest that bone also acts as an endocrine organ to regulate whole-body metabolism. Particularly, homeostasis of the bone is shown to be necessary for brain development and function. Abnormal bone metabolism is associated with the onset and progression of neurological disorders. Recently, multiple bone-derived modulators have been shown to participate in brain function and neurological disorders, including osteocalcin, lipocalin 2, and osteopontin, as have bone marrow-derived cells such as mesenchymal stem cells, hematopoietic stem cells, and microglia-like cells. This review summarizes current findings regarding the roles of these bone-derived modulators in the brain, and also follows their involvement in the pathogenesis of neurological disorders. The content of this review may aide in the development of promising therapeutic strategies for neurological disorders via targeting bone.
Highlights
The brain is a complex and powerful organ consisting of a great variety of nerve tissues that plays essential roles in coordinating body homeostasis (Qin et al, 2016)
The purpose of this review is to provide a detailed overview of the bone-derived modulators that have the capability to regulate brain functions, and to summarize the current knowledge about the relevance of the bone-derived modulators in the pathogenesis of neurological disorders
The results indicate that LCN2 may participate in the regulation of Alzheimer’s disease (AD) pathogenesis by influencing neuroinflammation, insulin signaling, and cellular responses associated with Aβ plaques
Summary
The brain is a complex and powerful organ consisting of a great variety of nerve tissues that plays essential roles in coordinating body homeostasis (Qin et al, 2016). Bone mainly regulates brain development, function, and pathophysiology by secreting various proteins, including OCN, lipocalin-2 (LCN2), and osteopontin (OPN) (Figure 1), and providing cells such as bone-derived mesenchymal stem cells (BMSCs), hematopoietic stem cells, and microglia-like cells (Otto et al, 2020). Maternal OCN was required for the fetal brain to regulate the progression of neurogenesis and prevent neuronal apoptosis, and it was necessary for optimal memory and spatial in the adult offspring (Oury et al, 2013) Another bone-derived hormone, LCN2, known as 24p3 and neutrophil gelatinase-associated lipocalin, is an osteoblastenriched glycoprotein (Borregaard and Cowland, 2006). The upregulation of LCN2 promotes the migration of microglia, astrocytes, and neurons, which play an important role in neuroinflammation
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