Contributors<br>Short biographies of the contributors<br>Preface<br><br>1. General aspects of extracellular vesicles in bone formation and remodeling <br>Antonio Maurizi and Anna Teti<br><br>1. Introduction <br>2. Communications between bone cells <br>3. Extracellular vesicles <br>4. Bone cell overview <br>5. Bone marrow cells interacting with skeletal cells <br>6. Extracellular vesicle trafficking in the bone microenvironment <br>7. Extracellular vesicles in fracture healing <br>8. Extracellular vesicles and bone cancer <br>9. Medical applications <br>10. Conclusions <br><br>List of abbreviations <br>Acknowledgments <br>References <br><br>2. Physiological biomineralization. The properties and role of matrix vesicles in skeletal and dental calcifications <br>René Buchet, Saida Mebarek, Slawomir Pikula, Agnieszka Strzelecka-Kiliszek, David Magne, Leticia Fernanda Duffles, Thaise Mayumi Taira, Massimo Bottini, Pietro Ciancaglini, José Luis Millán and Sandra Yasuyo Fukada<br><br>1. Introduction <br>2. Biomineralization in teeth <br>3. Biomineralization in bones <br>4. Determinants of mineralization support the functions of matrix vesicles <br>5. Conclusions <br><br>List of abbreviations <br>Acknowledgments <br>References <br><br>3. Pathological biomineralization. Part I: mineralizing extracellular vesicles in cardiovascular diseases <br>Rene Buchet, Slawomir Pikula, Agnieszka Strzelecka-Kiliszek, Massimo Bottini, Ana Paula Ramos, Pietro Ciancaglini, Jose Luis Millan and Saida Mebarek<br><br>1. Introduction <br>2. Extracellular vesicles: origin and classification <br>3. Extracellular vesicles related to cardiovascular diseases <br>4. Extracellular vesicles: biomarkers of cardiovascular diseases <br>5. Extracellular vesicles as drug delivery vehicles in cardiovascular disease<br>6. Conclusions<br><br>List of abbreviations <br>Acknowledgments <br>References<br><br>4. Pathologic biomineralization: part II: mineralizing extracellular vesicles in osteoarthritis <br>Ann K. Rosenthal<br><br>1. Introduction <br>2. Historical perspective <br>3. Characterization of ACVs <br>4. ACVs from osteoarthritis cartilage <br>5. Factors affecting ACV mineralization <br>6. Conclusions and future directions<br> <br>List of abbreviations <br>Acknowledgments <br>References <br><br>5. The biochemistry of mineralizing extracellular vesicles.<br>Part I: The role of phosphatases <br>Flavia Amadeu de Oliveira, Cintia Kazuko Tokuhara, Lucas Fabricio Bahia Nogueira, Juçara Gastaldi Cominal, Luiz Henrique da Silva Andrilli, Sonoko Narisawa, Colin Farquharson, Massimo Bottini, Ana Paula Ramos, Pietro Ciancaglini and José Luis Millán<br><br>1. Inorganic phosphate (Pi) and pyrophosphate (PPi): a physicochemical balance<br>2. The molecules regulating the Pi/PPi ratio <br>3. Tissue-nonspecific alkaline phosphatase <br>4. Ectonucleotide pyrophosphatase/phosphodiesterase 1 and other ENPPs<br>5. Nucleoside triphosphate diphosphohydrolase 1 (CD39) and ecto-50-nucleotidase (CD73)<br>6. PHOSPHO1 <br>7. Can Na,K-ATPase act as a phosphatase? <br>8. Phosphate transporters <br>9. Genetic diseases caused by altered Pi/PPi ratio<br>10. Therapeutic approaches to normalizing the Pi/PPi ratio<br>11. Conclusions<br><br>List of abbreviations <br>Acknowledgments <br>References<br><br>6. The biochemistry of mineralizing extracellular vesicles.<br>Part II: Annexins 127<br>Slawomir Pikula, Agnieszka Strzelecka-Kiliszek, René Buchet, Saida Mebarek, Laurence Bessueille, Thierry Granjon, David Magne, Lilianna Weremiejczyk, Agnieszka Kinga Seliga and Joanna Bandorowicz-Pikula<br><br>1. Introduction <br>2. Annexins <br>3. Annexin knockout animal models <br>4. Annexins in mineralization-competent cells <br>5. Annexins in media vesicles and matrix vesicles <br>6. In vitro properties of annexins <br>7. Conclusions <br><br>List of abbreviations <br>Acknowledgments <br>References <br><br>7. Calcium and phosphate and their role in matrix vesicles: A biological view <br>Larwsk Hayann, Pietro Ciancaglini, Ana Paula Ramos and Dobrawa Napierala<br><br>1. Calcium (Ca2þ) and inorganic phosphate (PO3/4-/Pi) ions are essential for life<br>2. Ca2þ and phosphate ions in mineralization physiology and pathology<br>3. Cellular origins of matrix vesicles<br>4. Formation of mineralization-competent matrix vesicles requires osteo/chondrogenic molecular phenotype of the cells<br>5. Conclusions <br><br>List of abbreviations <br>Acknowledgments<br>References<br><br>8. Autophagy in bone metabolism and its possible role on the function of mineralizing extracellular vesicles<br>Marcos A.E. Cruz, Heitor G. Sebinelli, Pietro Ciancaglini, Massimo Bottini and Ana Paula Ramos<br><br>1. Molecular overview of autophagy<br>2. The canonical role of autophagy on bone maintenance<br>3. The noncanonical role of autophagy on bone mineralization<br>4. The role of autophagy on the release of mineralizing extracellular vesicles<br>5. Induced autophagy decreases smooth muscles cells calcification<br>6. Conclusions <br><br>List of abbreviations <br>Acknowledgments<br>References<br><br>9. The roles of mineralizing extracellular vesicles in cellecell communication<br>Tomoko Minamizaki, Shohei Kohono and Yuji Yoshiko<br><br>1. Introduction <br>2. Proteins in mineralizing EVs <br>3. miRNAs in mineralizing EVs<br>4. Conclusion <br>List of abbreviations <br>Acknowledgments <br>References <br><br>10. Working with mineralizing extracellular vesicles.<br>Part I: Purification techniques <br>René Buchet, Slawomir Pikula, Agnieszka Strzelecka-Kiliszek, David Magne, Massimo Bottini and Saida Mebarek<br><br>1. Discovery of matrix vesicles <br>2. Purification of matrix vesicles from the growth plates and epiphyseal cartilage of chicken embryos <br>3. Purification of matrix vesicles from rodent primary chondrocytes <br>4. Purification of matrix vesicles from osteoblast cell lines and from primary osteoblasts <br>5. Conclusion <br><br>List of abbreviations <br>Acknowledgments <br>References <br><br>11. Working with mineralizing extracellular vesicles. <br>Part II: Proteomic profiling <br>René Buchet, Saida Mebarek, Agnieszka Strzelecka-Kiliszek, Massimo Bottini and Slawomir Pikula<br><br>1. Introduction <br>2. Essential proteins found prior to the proteomic analysis <br>3. Proteomic analysis of matrix vesicles extracted from growth plate cartilage of chicken embryo <br>4. Proteomic analysis of matrix vesicles extracted from osteoblast cell lines <br>5. Comparative analysis of proteomes of matrix vesicles and articular cartilage vesicles <br>6. Comparative analysis of matrix vesicles and of extracellular vesicles proteomes <br>7. Conclusions <br><br>List of Abbreviations<br>Acknowledgments<br>References<br><br>12. Working with mineralizing extracellular vesicles. <br>Part III: The nucleational core<br>Ana Paula Ramos, Marcos Antonio Eufrasio Cruz, Pietro Ciancaglini, Saida Mebarek, René Buchet, José Luis Millan and Massimo Bottini<br><br>1. Introduction<br>2. Physicochemical aspects of biomineralization<br>3. Discovery of the nucleational core<br>4. Isolation and characterization of the nucleational core <br>5. Parameters driving the formation of phosphatidylserine complexes and amorphous calcium phosphate <br>6. Use of the AFM in the characterization of the nucleational core<br>7. Conclusions <br><br>List of abbreviations <br>Acknowledgments <br>References <br><br>13. Working with mineralizing extracellular vesicles<br>Part IV: Biomimetic models <br>Maytê Bolean, Heitor G. Sebinelli, Luiz H.S. Andrilli, Bruno Z. Favarin, Ekeveliny A. Veschi, Marcos A.E. Cruz, Rene Buchet, Saida Mebarek, José Luis Millán, Massimo Bottini, Ana Paula Ramos and Pietro Ciancaglini<br><br>1. Introduction<br>2. Proteoliposomes as biomimetic models to assess the role of TNAP in biomineralization<br>3. Proteoliposomes as biomimetic models to assess the role of Naþ,Kþ-ATPase and NPP1 in biomineralization<br>4. Proteoliposomes as biomimetic models to assess the role of annexins in biomineralization<br>5. Langmuir films as biomimetic models of matrix vesicles<br>6. Conclusions <br><br>List of abbreviations <br>Acknowledgments <br>References <br><br>14. Working with mineralizing extracellular vesicles. <br>Part V: Use of Mineralizing extracellular vesicles in bone regeneration <br>Larwsk Hayann, Maryanne Trafani Melo, Lucas Fabricio Bahia Nogueira, Pietro Ciancaglini, Massimo Bottini and Ana Paula Ramos<br><br>1. Introduction<br>2. Biogenesis of extracellular vesicles<br>3. Matrix vesicles: A special class of extracellular vesicles<br>4. Conclusions<br><br>List of abbreviations<br>Acknowledgments<br>References<br><br>Index