osteoprotegerin and Multiple-Sclerosis

The high prevalence of osteoporosis, observed in multiple sclerosis (MS) patients, has been attributed to reduced mobility and or the use of disease-modifying drugs. However, MS-impaired cardiovascular autonomic nervous system (ANS) function has the potential of reducing bone mass density (BMD) by altering the expression and/or function of the neuronal, systemic, and local mediators of bone remodeling. This review describes the complex regulation of bone homeostasis with a focus on MS, providing evidence that ANS dysfunction and low BMD are intertwined with MS inflammatory and neurodegenerative processes, and with other MS-related morbidities, including depression, fatigue, and migraine. Strategies for improving ANS function could reduce the prevalence of MS osteoporosis and slow the rate of MS progression, with a significant positive impact on patients' quality of life.

Topics: Adiponectin; Autonomic Nervous System; Bone Density; Bone Remodeling; Brain; Cardiovascular System; Depression; Endocannabinoids; Fatigue; Humans; Inflammation; Leptin; Migraine Disorders; Multiple Sclerosis; Nerve Degeneration; Neuropeptide Y; Osteocalcin; Osteopontin; Osteoporosis; Osteoprotegerin; Parathyroid Hormone; RANK Ligand; Serotonin; Vitamin D

Women with multiple sclerosis (MS) can safely become pregnant and give birth, with no side effects or impediments. Pregnancy is generally accepted as a period of well-being in which relapses have a softer evolution, particularly in the third trimester. Herein, we hypothesized that the placenta, via its "secretome", could contribute to the recognized beneficial effects of pregnancy on MS activity. We focused on a well-known receptor/ligand/decoy receptor system, such as the one composed by the receptor activator of nuclear factor-kB (RANK), its ligand (RANKL), and the decoy receptor osteoprotegerin (OPG), which have never been investigated in an integrated way in MS, pregnancy, and placenta. We reported that pregnancy at the term of gestation influences the balance between circulating RANKL and its endogenous inhibitor OPG in MS women. We demonstrated that the placenta at term is an invaluable source of homodimeric OPG. By functional studies on astrocytes, we showed that placental OPG suppresses the mRNA expression of the CCL20, a chemokine responsible for Th17 cell recruitment. We propose placental OPG as a crucial molecule for the recognized beneficial effect of late pregnancy on MS and its potential utility for the development of new and more effective therapeutic approaches.

Topics: Female; Humans; Ligands; Multiple Sclerosis; Osteoprotegerin; Placenta; Pregnancy; Protein Binding; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B

Topics: Adult; Bone Remodeling; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Osteoprotegerin; RANK Ligand; Risk Factors

Topics: Adolescent; Adult; Age Factors; Blotting, Northern; Brain; Carrier Proteins; Female; Glycoproteins; Humans; Male; Membrane Glycoproteins; Middle Aged; Multiple Sclerosis; Nervous System Diseases; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; RNA, Messenger; Spinal Cord