osteoprotegerin and Acidosis

Bone health, characterized by its mass, density, and micro-architectural qualities, is maintained by a balanced system of remodeling. The lack of these qualities, caused by an uncoupling of the remodeling process, leads to bone fragility and an increased risk for fracture. The prime regulator of bone remodeling is the RANK/RANKL/OPG system. The common origin of both bone and immune stem cells is the key to understanding this system and its relationship to the transcription factor nuclear factor kappaB in bone loss and inflammation. Via this coupled osteo-immune relationship, a catabolic environment from heightened proinflammatory cytokine expression and/or a chronic antigen-induced activation of the immune system can initiate a switch-like diversion of osteoprogenitor-cell differentiation away from monocyte-macrophage and osteoblast cell formation and toward osteoclast and adipocyte formation. This disruption in bone homeostasis leads to increased fragility. Dietary and specific nutrient interventions can reduce inflammation and limit this diversion. Common laboratory biomarkers can be used to assess changes in body metabolism that affect bone health. This literature review offers practical information for applying effective strategic nutrition to fracture-risk individuals while monitoring metabolic change through serial testing of biomarkers. As examples, the clinician may recommend vitamin K and potassium to reduce hypercalciuria, _-lipoic acid and N-acetylcysteine to reduce the bone resorption marker N-telopeptide (N-Tx), and dehydroepiandrosterone (DHEA), whey, and milk basic protein (the basic protein fraction of whey) to increase insulin-like growth factor-1 (IGF-1) and create a more anabolic profile.

Topics: Absorptiometry, Photon; Acidosis; Biomarkers; Bone Density; Bone Remodeling; C-Reactive Protein; Calcium; Celiac Disease; Dehydroepiandrosterone; Female; Gonadal Steroid Hormones; Humans; Hydrocortisone; Hyperhomocysteinemia; Male; Osteoporosis; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Thyroid Diseases; Vitamin D; Vitamin K

Osteoblasts and osteoclasts maintain bone volume. Acidosis affects the function of these cells including mineral metabolism. We examined the effect of acidosis on the expression of transcription factors and mineralization in human osteoblasts in vitro. Human osteoblasts (SaM-1 cells) derived from the ulnar periosteum were cultured with α-MEM containing 50 μg/ml ascorbic acid and 5 mM β-glycerophosphate (calcifying medium). Acidosis was induced by incubating the SaM-1 cells in 10 % CO₂ (pH approximately 7.0). Mineralization, which was augmented by the calcifying medium, was completely inhibited by acidosis. Acidosis depressed c-Jun mRNA and increased osteoprotegerin (OPG) production in a time-dependent manner. Depressing c-Jun mRNA expression using siRNA increased OPG production and inhibited mineralization. In addition, depressing OPG mRNA expression with siRNA enhanced mineralization in a dose-dependent manner. Acidosis or the OPG protein strongly inhibited mineralization in osteoblasts from neonatal mice. The present study was the first to demonstrate that acidosis inhibited mineralization, depressed c-Jun mRNA expression, and induced OPG production in human osteoblasts. These results suggest that OPG is involved in mineralization via c-Jun in human osteoblasts.

Topics: Acidosis; Animals; Calcification, Physiologic; Cell Differentiation; Cells, Cultured; Culture Media; Cytokines; Glycerophosphates; Humans; Male; Mice; Mice, Inbred C57BL; Organic Chemicals; Osteoblasts; Osteoprotegerin; Periosteum; Proto-Oncogene Proteins c-jun; RANK Ligand; RNA, Messenger; RNA, Small Interfering; Time Factors; Ulna

Topics: Acidosis; Analgesics; Animals; Antineoplastic Agents; Atrasentan; Bone Neoplasms; Diphosphonates; Disease Models, Animal; Glycoproteins; Humans; Ion Channels; Neoplasms; Osteoprotegerin; Pain; Pyrrolidines; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor