Irma Machuca-Gayet1, Justine Bacchetta1,2,3,4, Julie Bernardor5,6,7,8,9, Candide Alioli1, Marie-Noelle Meaux1, Olivier Peyruchaud1. 1. INSERM, UMR 1033, Faculté de Médecine Lyon Est, Université Claude Bernard Lyon1, Lyon, France. 2. Centre de Référence des Maladies Rares du Calcium et du Phosphate, Filière Maladies Rares OSCAR, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France. 3. Centre de Référence des Maladies Rénales Rares, Filières Maladies Rares ORKID et ERK-Net, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France. 4. Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, France. 5. INSERM, UMR 1033, Faculté de Médecine Lyon Est, Université Claude Bernard Lyon1, Lyon, France. bernardor.j@chu-nice.fr. 6. Centre de Référence des Maladies Rares du Calcium et du Phosphate, Filière Maladies Rares OSCAR, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France. bernardor.j@chu-nice.fr. 7. Centre de Référence des Maladies Rénales Rares, Filières Maladies Rares ORKID et ERK-Net, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France. bernardor.j@chu-nice.fr. 8. Faculté de Médecine, Université de Nice Côte d'Azur, Nice, France. bernardor.j@chu-nice.fr. 9. Unité d'hémodialyse pédiatrique, Archet 2, CHU de Nice, 06202, Nice, France. bernardor.j@chu-nice.fr.
Abstract
PURPOSE OF REVIEW: To describe the methods that can be used to obtain functional and mature osteoclasts from peripheral blood mononuclear cells (PBMCs) and report the data obtained with this model in two peculiar diseases, namely pediatric chronic kidney disease-associated mineral and bone disorders (CKD-MBD) and nephropathic cystinosis. To discuss future research possibilities in the field. RECENT FINDINGS: Bone tissue undergoes continuous remodeling throughout life to maintain bone architecture; it involves two processes: bone formation and bone resorption with the coordinated activity of osteoblasts, osteoclasts, and osteocytes. Animal models fail to fully explain human bone pathophysiology during chronic kidney disease, mainly due to interspecies differences. The development of in vitro models has permitted to mimic human bone-related diseases as an alternative to in vivo models. Since 1997, osteoclasts have been generated in cell cultures, notably when culturing PBMCs with specific growth factors and cytokines (i.e., M-CSF and RANK-L), without the need for osteoblasts or stromal cells. These models may improve the global understanding of bone pathophysiology. They can be been used not only to evaluate the direct effects of cytokines, hormones, cells, or drugs on bone remodeling during CKD-MBD, but also in peculiar genetic renal diseases inducing specific bone impairment.
PURPOSE OF REVIEW: To describe the methods that can be used to obtain functional and mature osteoclasts from peripheral blood mononuclear cells (PBMCs) and report the data obtained with this model in two peculiar diseases, namely pediatric chronic kidney disease-associated mineral and bone disorders (CKD-MBD) and nephropathic cystinosis. To discuss future research possibilities in the field. RECENT FINDINGS: Bone tissue undergoes continuous remodeling throughout life to maintain bone architecture; it involves two processes: bone formation and bone resorption with the coordinated activity of osteoblasts, osteoclasts, and osteocytes. Animal models fail to fully explain human bone pathophysiology during chronic kidney disease, mainly due to interspecies differences. The development of in vitro models has permitted to mimic human bone-related diseases as an alternative to in vivo models. Since 1997, osteoclasts have been generated in cell cultures, notably when culturing PBMCs with specific growth factors and cytokines (i.e., M-CSF and RANK-L), without the need for osteoblasts or stromal cells. These models may improve the global understanding of bone pathophysiology. They can be been used not only to evaluate the direct effects of cytokines, hormones, cells, or drugs on bone remodeling during CKD-MBD, but also in peculiar genetic renal diseases inducing specific bone impairment.
Authors: Antonia Thiel; Marie K Reumann; Adele Boskey; Johannes Wischmann; Rüdiger von Eisenhart-Rothe; Philipp Mayer-Kuckuk Journal: Biol Rev Camb Philos Soc Date: 2017-06-19
Authors: Guiti Z Eghbali-Fatourechi; Jesse Lamsam; Daniel Fraser; David Nagel; B Lawrence Riggs; Sundeep Khosla Journal: N Engl J Med Date: 2005-05-12 Impact factor: 91.245