Bone remodeling in the context of cellular and systemic regulation: the role of osteocytes and the nervous system

Abstract

Bone is a dynamic tissue that undergoes constant remodeling. The appropriate course of this process determines development and regeneration of the skeleton. Tight molecular control of bone remodeling is vital for the maintenance of appropriate physiology and microarchitecture of the bone, providing homeostasis, also at the systemic level. The process of remodeling is regulated by a rich innervation of the skeleton, being the source of various growth factors, neurotransmitters, and hormones regulating function of the bone. Although the course of bone remodeling at the cellular level is mainly associated with the activity of osteoclasts and osteoblasts, recently also osteocytes have gained a growing interest as the principal regulators of bone turnover. Osteocytes play a significant role in the regulation of osteogenesis, releasing sclerostin (SOST), an inhibitor of bone formation. The process of bone turnover, especially osteogenesis, is also modulated by extra-skeletal molecules. Proliferation and differentiation of osteoblasts are promoted by the brain-derived serotonin and hypothetically inhibited by its intestinal equivalent. The activity of SOST and serotonin is either directly or indirectly associated with the canonical Wnt/β-catenin signaling pathway, the main regulatory pathway of osteoblasts function. The impairment of bone remodeling may lead to many skeletal diseases, such as high bone mass syndrome or osteoporosis. In this paper, we review the most recent data on the cellular and molecular mechanisms of bone remodeling control, with particular emphasis on the role of osteocytes and the nervous system in this process.

Prevention of muscle wasting and osteoporosis: the value of examining novel animal models

“…Bone remodelling is regulated by rich innervation of the skeleton, providing a source of various hormones, growth factors and neurotransmitters that modulate various functions of bone. For recent reviews on this topic, see Niedzwiedzki and Filipowska (2015) and Quiros-Gonzalez and Yadav (2014). Important extraskeletal compounds that are relevant to this Review and which can regulate bone remodelling include serotonin and the hormone leptin.…”

Natural Rubber Latex Biomaterials in Bone Regenerative Medicine

“…Ten to fifteen percent of total cardiac output goes to skeletal system [46]. The role of the blood vessels in the bone is not only to supply the bones with oxygen and nutrients but also to provide them with growth factor, hormones and neurotransmitters (e.g., brain-derived serotonin), maintaining the bone activity and cell survivor [47,48].…”

“…Osteoclasts form a cutting cone that moves forward resorbing dead bone or damaged/old bone matrix. A blood vessel follows this cutting cone, delivering nutrients, hormones and growth factors to osteoblast that will produce new bone [48]. OSX-expressing osteoblast precursors are involved in the process of remodeling, accompanying the blood vessels, positioning themselves in a perivascular localization, showing the tight relationship between osteogenesis and angiogenesis [54].…”

Synthetic and Marine-Derived Porous Bone Graft Substitutes

“…It possesses a unique self-regeneration capacity, which, in many cases, enables bone injuries and fractures heal without scar formation by responding to metabolic needs and adapting to the mechanical stresses applied to the tissue. This process is fundamental to maintain an adequate bone mass, appropriate mechanical properties, and the integrity of the skeleton [3,[42][43][44].…”

“…Indeed, it is precisely in the third decade when bone mass is at the maximum, and this is maintained with small variations until the age of 50. Posteriorly, resorption predominates and bone mass start to decrease [3,40,43].…”