|
1
|
Shapiro IM, Risbud MV, Tang T, Landis WJ. Skeletal and dental tissue mineralization: The potential role of the endoplasmic reticulum/Golgi complex and the endolysosomal and autophagic transport systems. Bone 2025; 193:117390. [PMID: 39814250 DOI: 10.1016/j.bone.2025.117390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/07/2025] [Accepted: 01/08/2025] [Indexed: 01/18/2025]
Abstract
This paper presents a review of the potential role of the endoplasmic reticulum/Golgi complex and intracellular vesicles in mediating events leading to or associated with vertebrate tissue mineralization. The possible importance of these organelles in this process is suggested by observations that calcium ions accumulate in the tubules and lacunae of the endoplasmic reticulum and Golgi. Similar levels of calcium ions (approaching millimolar) are present in vesicles derived from endosomes, lysosomes and autophagosomes. The cellular level of phosphate ions in these organelles is also high (millimolar). While the source of these ions for mineral formation has not been identified, there are sound reasons for considering that they may be liberated from mitochondria during the utilization of ATP for anabolic purposes, perhaps linked to matrix synthesis. Published studies indicate that calcium and phosphate ions or their clusters contained as cargo within the intracellular organelles noted above lead to formation of extracellular mineral. The mineral sequestered in mitochondria has been documented as an amorphous calcium phosphate. The ion-, ion cluster- or mineral-containing vesicles exit the cell in plasma membrane blebs, secretory lysosomes or possibly intraluminal vesicles. Such a cell-regulated process provides a means for the rapid transport of ions or mineral particles to the mineralization front of skeletal and dental tissues. Within the extracellular matrix, the ions or mineral may associate to form larger aggregates and potential mineral nuclei, and they may bind to collagen and other proteins. How cells of hard tissues perform their housekeeping and other biosynthetic functions while transporting the very large volumes of ions required for mineralization of the extracellular matrix is far from clear. Addressing this and related questions raised in this review suggests guidelines for further investigations of the intracellular processes promoting the mineralization of the skeletal and dental tissues.
Collapse
Affiliation(s)
- Irving M Shapiro
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States of America.
| | - Makarand V Risbud
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States of America
| | - Tengteng Tang
- Center for Applied Biomechanics, Department of Mechanical and Aerospace Engineering, School of Engineering and Applied Science, University of Virginia, Charlottesville, VA, United States of America
| | - William J Landis
- Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California at San Francisco, San Francisco, CA, United States of America
| |
Collapse
|
|
2
|
Dong H, Wang D, Deng H, Yin L, Wang X, Yang W, Cai K. Application of a calcium and phosphorus biomineralization strategy in tooth repair: a systematic review. J Mater Chem B 2024; 12:8033-8047. [PMID: 39045831 DOI: 10.1039/d4tb00867g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2024]
Abstract
Biomineralization is a natural process in which organisms regulate the growth of inorganic minerals to form biominerals with unique layered structures, such as bones and teeth, primarily composed of calcium and phosphorus. Tooth decay significantly impacts our daily lives, and the key to tooth regeneration lies in restoring teeth through biomimetic approaches, utilizing mineralization strategies or materials that mimic natural processes. This review delves into the types, properties, and transformations of calcium and phosphorus minerals, followed by an exploration of the mechanisms behind physiological and pathological mineralization in living organisms. It summarizes the mechanisms and commonalities of biomineralization and discusses the advancements in dental biomineralization research, guided by insights into calcium and phosphorus mineral biomineralization. This review concludes by addressing the current challenges and future directions in the field of dental biomimetic mineralization.
Collapse
Affiliation(s)
- Haide Dong
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China.
- Dencare (Chongqing) Oral Care Co., Ltd, Chongqing, People's Republic of China
| | - Danyang Wang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China.
| | - Hanyue Deng
- Duke Kunshan University - Media Art - Creative Practice Kunshan, Jiangsu 215316, China
| | - Lijuan Yin
- Dencare (Chongqing) Oral Care Co., Ltd, Chongqing, People's Republic of China
| | - Xiongying Wang
- Dencare (Chongqing) Oral Care Co., Ltd, Chongqing, People's Republic of China
| | - Weihu Yang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China.
| | - Kaiyong Cai
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China.
| |
Collapse
|
|
3
|
Jomaa Y, Aitisha-Tabesh O, Dgheim D, Faddoul R, Haddad-Zebouni S, Fayad F. Association of calcific rotator cuff tendinopathy with nephrolithiasis and/or cholelithiasis: A case-control study. Medicine (Baltimore) 2024; 103:e38482. [PMID: 38847678 PMCID: PMC11155589 DOI: 10.1097/md.0000000000038482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 05/16/2024] [Indexed: 06/10/2024] Open
Abstract
This study aimed to examine the association between calcific rotator cuff tendinopathy (RCT) and nephrolithiasis and/or cholelithiasis. A case-control study was conducted on patients diagnosed with RCT between June 2016 and June 2022. RCT was confirmed by ultrasound, and patients were divided into 2 groups: calcific RCT (case) and non-calcific RCT (control). Data were collected retrospectively from electronic medical records and completed by phone calls, looking for a history of nephrolithiasis and/or cholelithiasis; based on clinical features or incidental findings on abdominal and pelvic imaging. A total of 210 patients with RCT were included. Among the 95 cases of calcific RCT, 43 had a history of lithiasis (45.3%) against 23 (20%) from the non-calcific RCT group (P < .001); 21 patients suffered from nephrolithiasis (22.1%) and 26 had cholelithiasis (27.4%) versus 10 (8.7%) (P = .006) and 16 (13.9%) (P = .015) in the non-calcific RCT group, respectively. Logistic regression showed that the independent predictors of calcific RCT included a history of nephrolithiasis (OR, 4.38; 95% CI: 1.61-11.92, P = .004) and a history of cholelithiasis (OR, 3.83; 95% CI: 1.64-8.94, P = .002). In patients with calcific RCT, the occurrence of lithiasis was significantly associated in the bivariate analysis with higher age, body mass index, fasting blood sugar, and HbA1c (all with P < .05), but only with the presence of another site of calcific tendinopathy than the shoulder (OR, 3.11; 95% CI: 1.12-8.65, P = .03) in the multivariate analysis. Nephrolithiasis and/or cholelithiasis are associated with calcific RCT, and their presence predicts calcific RCT at least 3 times. Further research is required to determine the common risk factors and preventive measures against lithogenesis in patients with calcific RCT, nephrolithiasis, and cholelithiasis.
Collapse
Affiliation(s)
- Yara Jomaa
- Department of Anesthesiology, Hotel Dieu de France Hospital, Saint Joseph University of Beirut, Beirut, Lebanon
| | - Ouidade Aitisha-Tabesh
- Department of Rheumatology, Lebanese Hospital Geitaoui-UMC, Faculty of Medical Sciences, Lebanese University, Hadat, Lebanon
| | - Dima Dgheim
- Department of Rheumatology, Hotel Dieu de France Hospital, Saint Joseph University of Beirut, Beirut, Lebanon
| | - Rafic Faddoul
- ESIB Department, Saint Joseph University of Beirut, Beirut, Lebanon
| | - Soha Haddad-Zebouni
- Department of Radiology, Hotel Dieu de France Hospital, Saint Joseph University of Beirut, Beirut, Lebanon
| | - Fouad Fayad
- Department of Rheumatology, Lebanese Hospital Geitaoui-UMC, Faculty of Medical Sciences, Lebanese University, Hadat, Lebanon
| |
Collapse
|
|
4
|
Bielak K, Benkowska-Biernacka D, Ptak M, Stolarski J, Kalka M, Ożyhar A, Dobryszycki P. Otolin-1, an otolith- and otoconia-related protein, controls calcium carbonate bioinspired mineralization. Biochim Biophys Acta Gen Subj 2023; 1867:130327. [PMID: 36791829 DOI: 10.1016/j.bbagen.2023.130327] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 01/23/2023] [Accepted: 02/08/2023] [Indexed: 02/16/2023]
Abstract
BACKGROUND Otoliths and otoconia are calcium carbonate biomineral structures that form in the inner ear of fish and humans, respectively. The formation of these structures is tightly linked to the formation of an organic matrix framework with otolin-1, a short collagen-like protein from the C1q family as one of its major constituents. METHODS In this study, we examined the activity of recombinant otolin-1 originating from Danio rerio and Homo sapiens on calcium carbonate bioinspired mineralization with slow-diffusion method and performed crystals characterization with scanning electron microscopy, two-photon excited fluorescence microscopy, confocal laser scanning microscopy and micro-Raman spectroscopy. RESULTS We show that both proteins are embedded in the core of CaCO3 crystals that form through the slow-diffusion mineralization method. Both of them influence the morphology but do not change the polymorphic mineral phase. D.rerio otolin-1 also closely adheres to the crystal surface. GENERAL SIGNIFICANCE The results suggest, that otolin-1 is not a passive scaffold, but is directly involved in regulating the morphology of the resulting calcium carbonate biocrystals.
Collapse
Affiliation(s)
- Klaudia Bielak
- Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370 Wroclaw, Poland
| | - Dominika Benkowska-Biernacka
- Institute of Advanced Materials, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland
| | - Maciej Ptak
- Division of Optical Spectroscopy, Institute of Low Temperature and Structure Research, Polish Academy of Sciences, ul. Okólna 2, 50-422 Wroclaw, Poland
| | - Jarosław Stolarski
- Institute of Paleobiology, Polish Academy of Sciences, ul. Twarda 51/55, 00-818 Warsaw, Poland
| | - Marta Kalka
- Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370 Wroclaw, Poland
| | - Andrzej Ożyhar
- Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370 Wroclaw, Poland
| | - Piotr Dobryszycki
- Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370 Wroclaw, Poland.
| |
Collapse
|
|
5
|
Mitochondrial Dysfunction and Oxidative Stress in Hereditary Ectopic Calcification Diseases. Int J Mol Sci 2022; 23:ijms232315288. [PMID: 36499615 PMCID: PMC9738718 DOI: 10.3390/ijms232315288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 11/26/2022] [Accepted: 12/01/2022] [Indexed: 12/08/2022] Open
Abstract
Ectopic calcification (EC) is characterized by an abnormal deposition of calcium phosphate crystals in soft tissues such as blood vessels, skin, and brain parenchyma. EC contributes to significant morbidity and mortality and is considered a major health problem for which no effective treatments currently exist. In recent years, growing emphasis has been placed on the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of EC. Impaired mitochondrial respiration and increased levels of reactive oxygen species can be directly linked to key molecular pathways involved in EC such as adenosine triphosphate homeostasis, DNA damage signaling, and apoptosis. While EC is mainly encountered in common diseases such as diabetes mellitus and chronic kidney disease, studies in rare hereditary EC disorders such as pseudoxanthoma elasticum or Hutchinson-Gilford progeria syndrome have been instrumental in identifying the precise etiopathogenetic mechanisms leading to EC. In this narrative review, we describe the current state of the art regarding the role of mitochondrial dysfunction and oxidative stress in hereditary EC diseases. In-depth knowledge of aberrant mitochondrial metabolism and its local and systemic consequences will benefit the research into novel therapies for both rare and common EC disorders.
Collapse
|
|
6
|
Verminderte Mineralisation des Knochens: Rachitis und Osteomalazie. Monatsschr Kinderheilkd 2022. [DOI: 10.1007/s00112-021-01392-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
ZusammenfassungDie Mineralisation der Wachstumsfuge und des Knochens benötigt suffiziente Mengen an Kalzium und Phosphat, um ein adäquates Körperwachstum und eine adäquate Knochenstärke zu gewährleisten. Bei Mangelzuständen nehmen Härte und Stärke des Knochens ab (Osteomalazie), mit typischen Veränderungen an der Wachstumsfuge (Rachitis). Die vermeidbaren Komplikationen einer erworbenen Rachitis können lebensbedrohlich sein und sind auch deshalb ein global wichtiges Public-Health-Thema. Typische klinische Zeichen, Laborparameter und radiologische Veränderungen sollten zur unverzüglichen Diagnose führen. Erbliche und erworbene Formen der Rachitis wie X‑chromosomale Hypophosphatämie oder Hypophosphatasie werden, wie oftmals bei seltenen Erkrankungen, spät diagnostiziert. Diagnose, Therapie und Management von Rachitiden sollten durch tertiäre kinderosteologische Spezialisten erfolgen, die in internationalen „Rare-diseases“-Netzwerken arbeiten und in enger Kooperation mit Selbsthilfegruppen stehen.
Collapse
|
|
7
|
The Pulp Stones: Morphological Analysis in Scanning Electron Microscopy and Spectroscopic Chemical Quantification. MEDICINA (KAUNAS, LITHUANIA) 2021; 58:medicina58010005. [PMID: 35056314 PMCID: PMC8778352 DOI: 10.3390/medicina58010005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 12/16/2021] [Accepted: 12/17/2021] [Indexed: 12/26/2022]
Abstract
Background and objectives: Pulp stones are hard tissue structures formed in the pulp of permanent and deciduous teeth. Few studies have evaluated their morphology and chemical composition. However, their formation, composition, configuration and role played in overall health status are still unclear. Clinically, they may be symptomatic; technically, they impede access during endodontic therapy, increasing the risk of treatment errors. Thus, this study aimed to morphologically analyze pulp stones and present their chemical quantification, identifying their main chemical elements. It also correlates the results with their possible induction mechanisms. Materials and Methods: Seven pulp nodules were collected from molar teeth needing endodontic treatment. The morphology of the stones was analyzed by scanning electron microscopy (SEM), and their chemical composition was determined by X-ray dispersive energy spectroscopy (EDX). Results: These structures varied considerably in shape, size and topography. The site of the stones in the pulp cavity was the factor that most affected the morphology. The majority of the stones found in the pulp chambers presented nodular morphology, while those in the root canals presented a diffuse shape, resembling root canal anatomy. The topography of the nodules showed heterogeneous relief, revealing smooth and compact areas contrasting with the rugged and porous ones. The chemical composition varied depending on the location of the nodule in the pulp cavity and the relief of the analyzed area. Radicular stones presented considerably lower calcium and phosphorus content than coronary nodules. Conclusions: The high cellularity rate of the coronal pulp predisposes this region to nodular mineralizations around injured cells. The presence of larger caliber vascular bundles and higher collagen fiber content in radicular pulp determines a diffuse morphological pattern in this region. Understanding the morphology and chemical composition of the pulp stones allows future translational pathways towards the prevention or treatment of such conditions.
Collapse
|
|
8
|
Jaroszewicz J, Bazarnik P, Osiecka-Iwan A, Hyc A, Choinska E, Chlanda A, Swieszkowski W, Moskalewski S. From Matrix Vesicles to Miniature Rocks: Evolution of Calcium Deposits in Calf Costochondral Junctions. Cartilage 2021; 13:326S-335S. [PMID: 32672056 PMCID: PMC8804726 DOI: 10.1177/1947603520941225] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE Initial stages of cartilage matrix calcification depend on the activity of matrix vesicles. The purpose of the study was to describe how calcified matrix vesicles join into larger structures, to present their up-to-date undescribed 3-dimensional image, and to observe how calcified matrix relates to chondrocyte lacunae. DESIGN Calcified cartilage was obtained from the zone of provisional calcification of calf costochondral junctions, then enzymatically isolated and studied by microtomography, scanning electron microscopy, atomic force microscopy and X-ray diffraction, and Fourier transform infrared spectroscopy. RESULTS Hyaluronidase digestion released packets of granules surrounded by the cartilage matrix. Further digestion, with collagenase and trypsin, removed matrix and exposed granules with dimensions within 50 to 150 nm range, which we consider as equivalent of calcified matrix vesicles. Granules joined into larger groups with dimensions of 0.5 to 2 μm, which we call globular units. Certain matrix vesicles appeared well connected but contained globular units that had spaces filled with electron lucent material, presumably matrix or chondrocyte remnants. Globular units were organized into massive structures taking the shape of oval plates. Comparison of these plates with lacunae containing isogenous groups of chondrocytes from proliferative zone of costochondral junction suggests that the cells from a single lacuna were responsible for the formation of one plate. The plates were connected with each other and extended over provisional calcification zone. CONCLUSIONS The outcome showed how particular calcified matrix vesicles associate into globular units, which organize into massive structures assuming the shape of oval plates and eventually cover large areas of cartilage matrix.
Collapse
Affiliation(s)
- Jakub Jaroszewicz
- Faculty of Materials Science and
Engineering, Warsaw University of Technology, Warsaw, Poland,Jakub Jaroszewicz, Faculty of Materials
Science and Engineering, Warsaw University of Technology, Wołoska 141, Warsaw,
02-507, Poland.
| | - Piotr Bazarnik
- Faculty of Materials Science and
Engineering, Warsaw University of Technology, Warsaw, Poland
| | - Anna Osiecka-Iwan
- Department of Histology and Embryology,
Medical University of Warsaw, Warsaw, Poland
| | - Anna Hyc
- Department of Histology and Embryology,
Medical University of Warsaw, Warsaw, Poland
| | - Emilia Choinska
- Faculty of Materials Science and
Engineering, Warsaw University of Technology, Warsaw, Poland
| | - Adrian Chlanda
- Faculty of Materials Science and
Engineering, Warsaw University of Technology, Warsaw, Poland
| | - Wojciech Swieszkowski
- Faculty of Materials Science and
Engineering, Warsaw University of Technology, Warsaw, Poland
| | - Stanisław Moskalewski
- Department of Histology and Embryology,
Medical University of Warsaw, Warsaw, Poland
| |
Collapse
|
|
9
|
Abstract
Defective mineralization of the growth plate and preformed osteoid result in rickets and osteomalacia, respectively. The leading cause of rickets worldwide is solar vitamin D deficiency and/or dietary calcium deficiency collectively termed as nutritional rickets. Vitamin D deficiency predominates in high-latitude countries in at-risk groups (dark skin, reduced sun exposure, infants and pregnant and lactating women) but is emerging in some tropical countries due to sun avoidance behaviour. Calcium deficiency predominates in tropical countries, especially in the malnourished population. Nutritional rickets can have devastating health consequences beyond bony deformities (swollen wrist and ankle joints, rachitic rosary, soft skull, stunting and bowing) and include life-threatening hypocalcaemic complications of seizures and, in infancy, heart failure due to dilated cardiomyopathy. In children, diagnosis of rickets (always associated with osteomalacia) is confirmed on radiographs (cupping and flaring of metaphyses) and should be suspected in high risk individuals with the above clinical manifestations in the presence of abnormal blood biochemistry (high alkaline phosphatase and parathyroid hormone, low 25-hydroxyvitamin D and calcium and/or low phosphate). In adults or adolescents with closed growth plates, osteomalacia presents with non-specific symptoms (fatigue, malaise and muscle weakness) and abnormal blood biochemistry, but only in extreme cases, it is associated with radiographic findings of Looser's zone fractures. Bone biopsies could confirm osteomalacia at earlier disease stages, for definitive diagnosis. Treatment includes high-dose cholecalciferol or ergocalciferol daily for a minimum of 12 wk or stoss therapy in exceptional circumstances, each followed by lifelong maintenance supplementation. In addition, adequate calcium intake through diet or supplementation should be ensured. Preventative approaches should be tailored to the population needs and incorporate multiple strategies including targeted vitamin D supplementation of at-risk groups and food fortification with vitamin D and/or calcium. Economically, food fortification is certainly the most cost-effective way forward.
Collapse
Affiliation(s)
- Suma Uday
- Department of Endocrinology & Diabetes, Birmingham Women's & Children's NHS Foundation Trust; Institute of Metabolism & Systems Research, University of Birmingham, Edgbaston, Birmingham, UK
| | - Wolfgang Högler
- Institute of Metabolism & Systems Research, University of Birmingham, Edgbaston, Birmingham, UK; Department of Paediatrics & Adolescent Medicine, Johannes Kepler University, Kepler University Hospital, Med Campus IV, Linz, Austria
| |
Collapse
|
|
10
|
Boraldi F, Lofaro FD, Quaglino D. Apoptosis in the Extraosseous Calcification Process. Cells 2021; 10:cells10010131. [PMID: 33445441 PMCID: PMC7827519 DOI: 10.3390/cells10010131] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 01/07/2021] [Accepted: 01/10/2021] [Indexed: 12/13/2022] Open
Abstract
Extraosseous calcification is a pathologic mineralization process occurring in soft connective tissues (e.g., skin, vessels, tendons, and cartilage). It can take place on a genetic basis or as a consequence of acquired chronic diseases. In this last case, the etiology is multifactorial, including both extra- and intracellular mechanisms, such as the formation of membrane vesicles (e.g., matrix vesicles and apoptotic bodies), mitochondrial alterations, and oxidative stress. This review is an overview of extraosseous calcification mechanisms focusing on the relationships between apoptosis and mineralization in cartilage and vascular tissues, as these are the two tissues mostly affected by a number of age-related diseases having a progressively increased impact in Western Countries.
Collapse
Affiliation(s)
- Federica Boraldi
- Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy; (F.D.L.); (D.Q.)
- Correspondence:
| | - Francesco Demetrio Lofaro
- Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy; (F.D.L.); (D.Q.)
| | - Daniela Quaglino
- Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy; (F.D.L.); (D.Q.)
- Interuniversity Consortium for Biotechnologies (CIB), Italy
| |
Collapse
|
|
11
|
Fornaciari A, Gaeta R, Cavallini L, Aringhieri G, Ishak R, Bruschi F, Giuffra V. A 13th-century cystic echinococcosis from the cemetery of the monastery of Badia Pozzeveri (Lucca, Italy). INTERNATIONAL JOURNAL OF PALEOPATHOLOGY 2020; 31:79-88. [PMID: 33096379 DOI: 10.1016/j.ijpp.2020.10.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 10/06/2020] [Accepted: 10/11/2020] [Indexed: 06/11/2023]
Abstract
OBJECTIVE To differentially diagnose a calcified formation recovered from a 13th century AD grave from the Tuscan monastery of Badia Pozzeveri, Lucca, Italy. MATERIALS A calcified formation from the thoraco-abdominal region of a skeleton buried in the monastery cemetery. METHODS Cone Beam Computed Tomography, Scanning Electron Microscope and Energy Dispersive X-Ray Spectroscopy. RESULTS A hollow, calcified ovoid formation was identified as typical of a hydatid cyst, permitting the diagnosis of cystic echinococcosis in a 35-45year-old female. CONCLUSIONS The study reveals the circulation of the parasite Echinococcus granulosus in the region of Lucca in late medieval Tuscany. SIGNIFICANCE This finding is the fourth case of cystic echinococcosis from an archaeological context in Italy and provides insight into environmental conditions that appear to have affected members of a community, irrespective of social status. LIMITATIONS Caution and the application of multiple analyses must be exercised in the differential diagnosis to discriminate among calcified formations. SUGGESTIONS FOR FURTHER RESEARCH Analysis of stable isotopes of the calcified formation, such as 15N and 13C, in order to compare them with isotopic values of the host individual and to further confirm the parasitic origin of the find.
Collapse
Affiliation(s)
- Antonio Fornaciari
- Division of Paleopathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy.
| | - Raffaele Gaeta
- Division of Paleopathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy
| | - Letizia Cavallini
- Division of Paleopathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy
| | - Giacomo Aringhieri
- Diagnostic and Interventional Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy
| | - Randa Ishak
- Department of Civil and Industrial Engineering, University of Pisa, Italy
| | - Fabrizio Bruschi
- Laboratory of Parasitology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy
| | - Valentina Giuffra
- Division of Paleopathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy
| |
Collapse
|
|
12
|
Nie L, Li X, Wang Z, Hu K, Cai R, Li P, Han Y, Sun M, Yuan H, Suo J, Yang S. In vitro biomineralization on poly(vinyl alcohol)/biphasic calcium phosphate hydrogels. BIOINSPIRED BIOMIMETIC AND NANOBIOMATERIALS 2020. [DOI: 10.1680/jbibn.19.00051] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Biomineralized tissue is considered the final product of successful cell culture in bone tissue engineering. Dulbecco’s modified Eagle’s medium (DMEM) with fetal bovine serum (FBS) not only is used as a common culture medium but also provides a natural biomineralization environment, due to having similar ionic concentrations as blood plasma. Here, poly(vinyl alcohol) hydrogel with incorporated biphasic calcium phosphate nanoparticles was immersed in a DMEM–FBS cell culture medium, and then biomineralization occurred on the nanocomposite surface, which was characterized by Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy. Such formed bone-like apatite on the surface facilitated the proliferation of osteoblasts, identified by Cell Counting Kit-8 analysis and fluorescent microscopy. This study verified the spontaneous biomineralization on the surface of a calcium phosphate-based nanocomposite by using a simple DMEM–FBS immersion strategy, which was promising for biomodification of bone substitutes.
Collapse
Affiliation(s)
- Lei Nie
- College of Life Sciences, Xinyang Normal University, Xinyang, China
| | - Xingchen Li
- College of Life Sciences, Xinyang Normal University, Xinyang, China
| | - Zheng Wang
- College of Life Sciences, Xinyang Normal University, Xinyang, China
| | - Kehui Hu
- Department of Mechanical Engineering, Tsinghua University, Beijing, China
| | - Ruihua Cai
- College of Life Sciences, Xinyang Normal University, Xinyang, China
| | - Pei Li
- College of Life Sciences, Xinyang Normal University, Xinyang, China
| | - Yanting Han
- College of Life Sciences, Xinyang Normal University, Xinyang, China
| | - Meng Sun
- College of Life Sciences, Xinyang Normal University, Xinyang, China
| | - Hongyu Yuan
- College of Life Sciences, Xinyang Normal University, Xinyang, China
| | - Jinping Suo
- State Key Laboratory of Mould Technology, College of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, China
| | - Shoufeng Yang
- Department of Mechanical Engineering, Catholic University of Leuven, Leuven, Belgium
| |
Collapse
|
|
13
|
Bolean M, Izzi B, van Kerckhoven S, Bottini M, Ramos AP, Millán JL, Hoylaerts MF, Ciancaglini P. Matrix vesicle biomimetics harboring Annexin A5 and alkaline phosphatase bind to the native collagen matrix produced by mineralizing vascular smooth muscle cells. Biochim Biophys Acta Gen Subj 2020; 1864:129629. [PMID: 32360152 DOI: 10.1016/j.bbagen.2020.129629] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 04/13/2020] [Accepted: 04/28/2020] [Indexed: 10/24/2022]
Abstract
BACKGOUND Vascular smooth muscle cells (VSMCs) transdifferentiated ectopically trigger vascular calcifications, contributing to clinical cardiovascular disease in the aging population. AnxA5 and TNAP play a crucial role in (patho)physiological mineralization. METHODS We performed affinity studies between DPPC and 9:1 DPPC:DPPS-proteoliposomes carrying AnxA5 and/or TNAP and different types of collagen matrix: type I, II, I + III and native collagenous extracellular matrix (ECM) produced from VSMCs with or without differentiation, to simulate ectopic calcification conditions. RESULTS AnxA5-proteoliposomes had the highest affinity for collagens, specially for type II. TNAP-proteoliposomes bound poorly and the simultaneous presence of TNAP in the AnxA5-proteoliposomes disturbed interactions between AnxA5 and collagen. DPPC AnxA5-proteoliposomes affinities for ECM from transdifferentiating cells went up 2-fold compared to that from native VSMCs. The affinities of DPPC:DPPS-proteoliposomes were high for ECM from VSMCs with or without differentiation, underscoring a synergistic effect between AnxA5 and DPPS. Co-localization studies uncovered binding of proteoliposomes harboring AnxA5 or TNAP+AnxA5 to various regions of the ECM, not limited to type II collagen. CONCLUSION AnxA5-proteoliposomes showed the highest affinities for type II collagen, deposited during chondrocyte mineralization in joint cartilage. TNAP in the lipid/protein microenvironment disturbs interactions between AnxA5 and collagen. These findings support the hypothesis that TNAP is cleaved from the MVs membrane just before ECM binding, such facilitating MV anchoring to ECM via AnxA5 interaction. GENERAL SIGNIFICANCE Proteoliposomes as MV biomimetics are useful in the understanding of mechanisms that regulate the mineralization process and may be essential for the development of novel therapeutic strategies to prevent or inhibit ectopic mineralization.
Collapse
Affiliation(s)
- Maytê Bolean
- Department of Chemistry, FFCLRP-USP, University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Benedetta Izzi
- Department of Epidemiology and Prevention, IRCCS NEUROMED, Pozzilli, IS, Italy
| | | | - Massimo Bottini
- University of Rome Tor Vergata, Department of Experimental Medicine and Surgery, Roma, Italy; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
| | - Ana Paula Ramos
- Department of Chemistry, FFCLRP-USP, University of São Paulo, Ribeirão Preto, SP, Brazil
| | - José Luis Millán
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
| | - Marc F Hoylaerts
- Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
| | - Pietro Ciancaglini
- Department of Chemistry, FFCLRP-USP, University of São Paulo, Ribeirão Preto, SP, Brazil.
| |
Collapse
|
|
14
|
Roschger A, Wagermaier W, Gamsjaeger S, Hassler N, Schmidt I, Blouin S, Berzlanovich A, Gruber GM, Weinkamer R, Roschger P, Paschalis EP, Klaushofer K, Fratzl P. Newly formed and remodeled human bone exhibits differences in the mineralization process. Acta Biomater 2020; 104:221-230. [PMID: 31926334 DOI: 10.1016/j.actbio.2020.01.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 12/08/2019] [Accepted: 01/05/2020] [Indexed: 12/13/2022]
Abstract
During human skeletal growth, bone is formed via different processes. Two of them are: new bone formation by depositing bone at the periosteal (outer) surface and bone remodeling corresponding to a local renewal of tissue. Since in remodeling formation is preceded by resorption, we hypothesize that modeling and remodeling could require radically different transport paths for ionic precursors of mineralization. While remodeling may recycle locally resorbed mineral, modeling implies the transport over large distances to the site of bone apposition. Therefore, we searched for potential differences of size, arrangement and chemical composition of mineral particles just below surfaces of modeling and remodeling sites in femur midshaft cross-sections from healthy children. These bone sites were mapped using scanning synchrotron X-ray scattering, Raman microspectroscopy, energy dispersive X-ray analysis and quantitative backscattered electron microscopy. The results show clear differences in mineral particle size and composition between the sites, which cannot be explained by a change in the rate of mineral apposition or accumulation. At periosteal modeling sites, mineral crystals are distinctly larger, display higher crystallinity and exhibit a lower calcium to phosphorus ratio and elevated Na and Mg content. The latter may originate from Mg used for phase stabilization of mineral precursors and therefore indicate different time periods for mineral transport. We conclude that the mineralization process is distinctively different between modeling and remodeling sites due to varying requirements for the transport distance and, therefore, the stability of non-crystalline ionic precursors, resulting in distinct compositions of the deposited mineral phase. STATEMENT OF SIGNIFICANCE: In growing children new bone is formed either due to apposition of bone tissue e.g. at the outer ridge of long bones to allow growth in thickness (bone modeling), or in cavities inside the mineralized matrix when replacing tissue (bone remodeling). We demonstrate that mineral crystal shape and composition are not the same between these two sites, which is indicative of differences in mineralization precursors. We suggest that this may be due to a longer mineral transport distance to sites of new bone formation as compared to remodeling where mineral can be locally recycled.
Collapse
Affiliation(s)
- Andreas Roschger
- Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, D-14424 Potsdam, Germany; Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, A-1140 Vienna, Austria; Department for Chemistry and Physics of Materials, Paris Lodron University of Salzburg, Jakob-Haringer Straße 2a, 5020 Salzburg, Austria.
| | - Wolfgang Wagermaier
- Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, D-14424 Potsdam, Germany
| | - Sonja Gamsjaeger
- Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, A-1140 Vienna, Austria
| | - Norbert Hassler
- Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, A-1140 Vienna, Austria
| | - Ingo Schmidt
- Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, D-14424 Potsdam, Germany
| | - Stéphane Blouin
- Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, A-1140 Vienna, Austria
| | - Andrea Berzlanovich
- Department of Forensic Medicine, Medical University of Vienna, Sensengasse 2, A-1090 Vienna, Austria
| | - Gerlinde M Gruber
- Department of Anatomy, Center for Anatomy and Cell Biology, Medical University of Vienna, A-1090 Vienna
| | - Richard Weinkamer
- Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, D-14424 Potsdam, Germany
| | - Paul Roschger
- Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, A-1140 Vienna, Austria
| | - Eleftherios P Paschalis
- Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, A-1140 Vienna, Austria
| | - Klaus Klaushofer
- Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, A-1140 Vienna, Austria
| | - Peter Fratzl
- Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, D-14424 Potsdam, Germany
| |
Collapse
|
|
15
|
Clemente A, Traghella I, Mazzone A, Sbrana S, Vassalle C. Vascular and valvular calcification biomarkers. Adv Clin Chem 2020; 95:73-103. [PMID: 32122525 DOI: 10.1016/bs.acc.2019.08.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Vascular and valvular calcification constitutes a major health problem with serious clinical consequences. It is important for medical laboratorians to improve their knowledge on this topic and to know which biological markers may have a potential interest and might be useful for diagnosis and for management of ectopic calcifications. This review focuses on the pathophysiological mechanisms of vascular and valvular calcification, with emphasis on the mechanisms that are different for the two types of events, which underscore the need for differentiated healthcare, and explain different response to therapy. Available imaging and scoring tools used to assess both vascular and valvular calcification, together with the more studied and reliable biological markers emerging in this field (e.g., Fetuin A and matrix Gla protein), are discussed. Recently proposed functional assays, measuring the propensity of human serum to calcify, appear promising for vascular calcification assessment and are described. Further advancement through omic technologies and statistical tools is also reported. Clinical chemistry and laboratory medicine practitioners overlook this new era that will engage them in the near future, where a close cooperation of professionals with different competencies, including laboratorists, is required. This innovative approach may truly revolutionize practice of laboratory and of whole medicine attitude, making progression in knowledge of pathways relevant to health, as the complex calcification-related pathways, and adding value to patient care, through a precision medicine strategy.
Collapse
|
|
16
|
Exome sequencing and bioinformatic approaches reveals rare sequence variants involved in cell signalling and elastic fibre homeostasis: new evidence in the development of ectopic calcification. Cell Signal 2019; 59:131-140. [DOI: 10.1016/j.cellsig.2019.03.020] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2018] [Revised: 03/25/2019] [Accepted: 03/25/2019] [Indexed: 12/30/2022]
|
|
17
|
Verri T, Werner A. Type II Na +-phosphate Cotransporters and Phosphate Balance in Teleost Fish. Pflugers Arch 2018; 471:193-212. [PMID: 30542786 DOI: 10.1007/s00424-018-2239-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 11/15/2018] [Accepted: 11/18/2018] [Indexed: 12/27/2022]
Abstract
Teleost fish are excellent models to study the phylogeny of the slc34 gene family, Slc34-mediated phosphate (Pi) transport and how Slc34 transporters contribute Pi homeostasis. Fish need to accumulate Pi from the diet to sustain growth. Much alike in mammals, intestinal uptake in fish is partly a paracellular and partly a Slc34-mediated transcellular process. Acute regulation of Pi balance is achieved in the kidney via a combination of Slc34-mediated secretion and/or reabsorption. A great plasticity is observed in how various species perform and combine the different processes of secretion and reabsorption. A reason for this diversity is found in one or two whole genome duplication events followed by potential gene loss; consequently, teleosts exhibit distinctly different repertoires of Slc34 transporters. Moreover, due to habitats with vastly different salinity, teleosts face the challenge of either preserving water in a hyperosmotic environment (seawater) or excreting water in hypoosmotic freshwater. An additional challenge in understanding teleost Pi homeostasis are the genome duplication and retention events that diversified peptide hormones such as parathyroid hormone and stanniocalcin. Dietary Pi and non-coding RNAs also regulate the expression of piscine Slc34 transporters. The adaptive responses of teleost Slc34 transporters to e.g. Pi diets and vitamin D are informative in the context of comparative physiology, but also relevant in applied physiology and aquaculture. In fact, Pi is essential for teleost fish growth but it also exerts significant adverse consequences if over-supplied. Thus, investigating Slc34 transporters helps tuning the physiology of commercially valuable teleost fish in a confined environment.
Collapse
Affiliation(s)
- Tiziano Verri
- Laboratory of General Physiology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy.
| | - Andreas Werner
- Epithelial Research Group, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
| |
Collapse
|
|
18
|
Beck L. Expression and function of Slc34 sodium-phosphate co-transporters in skeleton and teeth. Pflugers Arch 2018; 471:175-184. [PMID: 30511265 DOI: 10.1007/s00424-018-2240-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 11/22/2018] [Accepted: 11/23/2018] [Indexed: 12/20/2022]
Abstract
Under normal physiological condition, the biomineralization process is limited to skeletal tissues and teeth and occurs throughout the individual's life. Biomineralization is an actively regulated process involving the progressive mineralization of the extracellular matrix secreted by osteoblasts in bone or odontoblasts and ameloblasts in tooth. Although the detailed molecular mechanisms underlying the formation of calcium-phosphate apatite crystals are still debated, it is suggested that calcium and phosphate may need to be transported across the membrane of the mineralizing cell, suggesting a pivotal role of phosphate transporters in bone and tooth mineralization. In this context, this short review describes the current knowledge on the role of Slc34 Na+-phosphate transporters in skeletal and tooth mineralization.
Collapse
Affiliation(s)
- Laurent Beck
- INSERM, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Faculté de Chirurgie Dentaire, Université de Nantes, ONIRIS, 1 place Alexis Ricordeau, 44042, Nantes, France. .,Université de Nantes, UFR Odontologie, 44042, Nantes, France.
| |
Collapse
|
|
19
|
Bottini M, Mebarek S, Anderson KL, Strzelecka-Kiliszek A, Bozycki L, Simão AMS, Bolean M, Ciancaglini P, Pikula JB, Pikula S, Magne D, Volkmann N, Hanein D, Millán JL, Buchet R. Matrix vesicles from chondrocytes and osteoblasts: Their biogenesis, properties, functions and biomimetic models. Biochim Biophys Acta Gen Subj 2018; 1862:532-546. [PMID: 29108957 PMCID: PMC5801150 DOI: 10.1016/j.bbagen.2017.11.005] [Citation(s) in RCA: 117] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 10/28/2017] [Accepted: 11/01/2017] [Indexed: 01/01/2023]
Abstract
BACKGROUND Matrix vesicles (MVs) are released from hypertrophic chondrocytes and from mature osteoblasts, the cells responsible for endochondral and membranous ossification. Under pathological conditions, they can also be released from cells of non-skeletal tissues such as vascular smooth muscle cells. MVs are extracellular vesicles of approximately 100-300nm diameter harboring the biochemical machinery needed to induce mineralization. SCOPE OF THE REVIEW The review comprehensively delineates our current knowledge of MV biology and highlights open questions aiming to stimulate further research. The review is constructed as a series of questions addressing issues of MVs ranging from their biogenesis and functions, to biomimetic models. It critically evaluates experimental data including their isolation and characterization methods, like lipidomics, proteomics, transmission electron microscopy, atomic force microscopy and proteoliposome models mimicking MVs. MAJOR CONCLUSIONS MVs have a relatively well-defined function as initiators of mineralization. They bind to collagen and their composition reflects the composition of lipid rafts. We call attention to the as yet unclear mechanisms leading to the biogenesis of MVs, and how minerals form and when they are formed. We discuss the prospects of employing upcoming experimental models to deepen our understanding of MV-mediated mineralization and mineralization disorders such as the use of reconstituted lipid vesicles, proteoliposomes and, native sample preparations and high-resolution technologies. GENERAL SIGNIFICANCE MVs have been extensively investigated owing to their roles in skeletal and ectopic mineralization. MVs serve as a model system for lipid raft structures, and for the mechanisms of genesis and release of extracellular vesicles.
Collapse
Affiliation(s)
- Massimo Bottini
- University of Rome Tor Vergata, Department of Experimental Medicine and Surgery, 00133 Roma, Italy; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
| | - Saida Mebarek
- Universite Lyon 1, UFR Chimie Biochimie, 69 622 Villeurbanne Cedex, France; ICBMS UMR 5246 CNRS, 69 622 Villeurbanne Cedex, France; INSA, Lyon, 69 622 Villeurbanne Cedex, France; CPE, Lyon, 69 622 Villeurbanne Cedex, France; Universite de Lyon, 69 622 Villeurbanne Cedex, France
| | - Karen L Anderson
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
| | - Agnieszka Strzelecka-Kiliszek
- Nencki Institute of Experimental Biology, Department of Biochemistry, Polish Academy of Sciences, 02-093 Warsaw, Poland
| | - Lukasz Bozycki
- Nencki Institute of Experimental Biology, Department of Biochemistry, Polish Academy of Sciences, 02-093 Warsaw, Poland
| | - Ana Maria Sper Simão
- Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, USP, Departamento de Química, 14040-901 Ribeirão Preto, SP, Brazil
| | - Maytê Bolean
- Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, USP, Departamento de Química, 14040-901 Ribeirão Preto, SP, Brazil
| | - Pietro Ciancaglini
- Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, USP, Departamento de Química, 14040-901 Ribeirão Preto, SP, Brazil
| | - Joanna Bandorowicz Pikula
- Nencki Institute of Experimental Biology, Department of Biochemistry, Polish Academy of Sciences, 02-093 Warsaw, Poland
| | - Slawomir Pikula
- Nencki Institute of Experimental Biology, Department of Biochemistry, Polish Academy of Sciences, 02-093 Warsaw, Poland
| | - David Magne
- Universite Lyon 1, UFR Chimie Biochimie, 69 622 Villeurbanne Cedex, France; ICBMS UMR 5246 CNRS, 69 622 Villeurbanne Cedex, France; INSA, Lyon, 69 622 Villeurbanne Cedex, France; CPE, Lyon, 69 622 Villeurbanne Cedex, France; Universite de Lyon, 69 622 Villeurbanne Cedex, France
| | - Niels Volkmann
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
| | - Dorit Hanein
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
| | - José Luis Millán
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
| | - Rene Buchet
- Universite Lyon 1, UFR Chimie Biochimie, 69 622 Villeurbanne Cedex, France; ICBMS UMR 5246 CNRS, 69 622 Villeurbanne Cedex, France; INSA, Lyon, 69 622 Villeurbanne Cedex, France; CPE, Lyon, 69 622 Villeurbanne Cedex, France; Universite de Lyon, 69 622 Villeurbanne Cedex, France.
| |
Collapse
|
|
20
|
Bolean M, Borin IA, Simão AMS, Bottini M, Bagatolli LA, Hoylaerts MF, Millán JL, Ciancaglini P. Topographic analysis by atomic force microscopy of proteoliposomes matrix vesicle mimetics harboring TNAP and AnxA5. BIOCHIMICA ET BIOPHYSICA ACTA. BIOMEMBRANES 2017; 1859:1911-1920. [PMID: 28549727 PMCID: PMC5793902 DOI: 10.1016/j.bbamem.2017.05.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 05/02/2017] [Accepted: 05/17/2017] [Indexed: 01/28/2023]
Abstract
Atomic force microscopy (AFM) is one of the most commonly used scanning probe microscopy techniques for nanoscale imaging and characterization of lipid-based particles. However, obtaining images of such particles using AFM is still a challenge. The present study extends the capabilities of AFM to the characterization of proteoliposomes, a special class of liposomes composed of lipids and proteins, mimicking matrix vesicles (MVs) involved in the biomineralization process. To this end, proteoliposomes were synthesized, composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phospho-l-serine (DPPS), with inserted tissue-nonspecific alkaline phosphatase (TNAP) and/or annexin V (AnxA5), both characteristic proteins of osteoblast-derived MVs. We then aimed to study how TNAP and AnxA5 insertion affects the proteoliposomes' membrane properties and, in turn, interactions with type II collagen, thus mimicking early MV activity during biomineralization. AFM images of these proteoliposomes, acquired in dynamic mode, revealed the presence of surface protrusions with distinct viscoelasticity, thus suggesting that the presence of the proteins induced local changes in membrane fluidity. Surface protrusions were measurable in TNAP-proteoliposomes but barely detectable in AnxA5-proteoliposomes. More complex surface structures were observed for proteoliposomes harboring both TNAP and AnxA5 concomitantly, resulting in a lower affinity for type II collagen fibers compared to proteoliposomes harboring AnxA5 alone. The present study achieved the topographic analysis of lipid vesicles by direct visualization of structural changes, resulting from protein incorporation, without the need for fluorescent probes.
Collapse
Affiliation(s)
- Maytê Bolean
- Depto. Química, FFCLRP-USP, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
| | - Ivana A Borin
- Depto. Química, FFCLRP-USP, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
| | - Ana M S Simão
- Depto. Química, FFCLRP-USP, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
| | - Massimo Bottini
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy; Inflammatory and Infectious Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
| | - Luis A Bagatolli
- MEMPHYS - Center for Biomembrane Physics, University of Southern Denmark, Odense, Denmark
| | - Marc F Hoylaerts
- Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
| | - José L Millán
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
| | - Pietro Ciancaglini
- Depto. Química, FFCLRP-USP, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
| |
Collapse
|
|
21
|
Abstract
During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix (ECM) by promoting the synthesis of hydroxyapatite (HA) seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Several lipid and proteins present in the membrane of the MVs mediate the interactions of MVs with the ECM and regulate the initial mineral deposition and posterior propagation. Among the proteins of MV membranes, ion transporters control the availability of phosphate and calcium needed for initial HA deposition. Phosphatases (orphan phosphatase 1, ectonucleotide pyrophosphatase/phosphodiesterase 1 and tissue-nonspecific alkaline phosphatase) play a crucial role in controlling the inorganic pyrophosphate/inorganic phosphate ratio that allows MV-mediated initiation of mineralization. The lipidic microenvironment can help in the nucleation process of first crystals and also plays a crucial physiological role in the function of MV-associated enzymes and transporters (type III sodium-dependent phosphate transporters, annexins and Na+/K+ ATPase). The whole process is mediated and regulated by the action of several molecules and steps, which make the process complex and highly regulated. Liposomes and proteoliposomes, as models of biological membranes, facilitate the understanding of lipid-protein interactions with emphasis on the properties of physicochemical and biochemical processes. In this review, we discuss the use of proteoliposomes as multiple protein carrier systems intended to mimic the various functions of MVs during the initiation and propagation of mineral growth in the course of biomineralization. We focus on studies applying biophysical tools to characterize the biomimetic models in order to gain an understanding of the importance of lipid-protein and lipid-lipid interfaces throughout the process.
Collapse
|
|
22
|
Abstract
PURPOSE OF REVIEW We give an update on the etiology and potential treatment options of rare inherited monogenic disorders associated with arterial calcification and calcific cardiac valve disease. RECENT FINDINGS Genetic studies of rare inherited syndromes have identified key regulators of ectopic calcification. Based on the pathogenic principles causing the diseases, these can be classified into three groups: (1) disorders of an increased extracellular inorganic phosphate/inorganic pyrophosphate ratio (generalized arterial calcification of infancy, pseudoxanthoma elasticum, arterial calcification and distal joint calcification, progeria, idiopathic basal ganglia calcification, and hyperphosphatemic familial tumoral calcinosis; (2) interferonopathies (Singleton-Merten syndrome); and (3) others, including Keutel syndrome and Gaucher disease type IIIC. Although some of the identified causative mechanisms are not easy to target for treatment, it has become clear that a disturbed serum phosphate/pyrophosphate ratio is a major force triggering arterial and cardiac valve calcification. Further studies will focus on targeting the phosphate/pyrophosphate ratio to effectively prevent and treat these calcific disease phenotypes.
Collapse
MESH Headings
- Abnormalities, Multiple/drug therapy
- Abnormalities, Multiple/genetics
- Abnormalities, Multiple/metabolism
- Aortic Diseases/drug therapy
- Aortic Diseases/genetics
- Aortic Diseases/metabolism
- Basal Ganglia Diseases/drug therapy
- Basal Ganglia Diseases/genetics
- Basal Ganglia Diseases/metabolism
- Calcinosis/drug therapy
- Calcinosis/genetics
- Calcinosis/metabolism
- Cartilage Diseases/drug therapy
- Cartilage Diseases/genetics
- Cartilage Diseases/metabolism
- Dental Enamel Hypoplasia/drug therapy
- Dental Enamel Hypoplasia/genetics
- Dental Enamel Hypoplasia/metabolism
- Diphosphates/metabolism
- Enzyme Replacement Therapy
- Gaucher Disease/drug therapy
- Gaucher Disease/genetics
- Gaucher Disease/metabolism
- Hand Deformities, Congenital/drug therapy
- Hand Deformities, Congenital/genetics
- Hand Deformities, Congenital/metabolism
- Humans
- Hyperostosis, Cortical, Congenital/drug therapy
- Hyperostosis, Cortical, Congenital/genetics
- Hyperostosis, Cortical, Congenital/metabolism
- Hyperphosphatemia/drug therapy
- Hyperphosphatemia/genetics
- Hyperphosphatemia/metabolism
- Interferons/metabolism
- Metacarpus/abnormalities
- Metacarpus/metabolism
- Muscular Diseases/drug therapy
- Muscular Diseases/genetics
- Muscular Diseases/metabolism
- Odontodysplasia/drug therapy
- Odontodysplasia/genetics
- Odontodysplasia/metabolism
- Osteoporosis/drug therapy
- Osteoporosis/genetics
- Osteoporosis/metabolism
- Phosphates/metabolism
- Progeria/drug therapy
- Progeria/genetics
- Progeria/metabolism
- Pseudoxanthoma Elasticum/drug therapy
- Pseudoxanthoma Elasticum/genetics
- Pseudoxanthoma Elasticum/metabolism
- Pulmonary Valve Stenosis/drug therapy
- Pulmonary Valve Stenosis/genetics
- Pulmonary Valve Stenosis/metabolism
- Vascular Calcification/drug therapy
- Vascular Calcification/genetics
- Vascular Calcification/metabolism
Collapse
Affiliation(s)
- Yvonne Nitschke
- Department of General Pediatrics, Münster University Children's Hospital, Albert-Schweitzer-Campus 1, D-48149, Münster, Germany
| | - Frank Rutsch
- Department of General Pediatrics, Münster University Children's Hospital, Albert-Schweitzer-Campus 1, D-48149, Münster, Germany.
| |
Collapse
|
|
23
|
Monge Calleja ÁM, Sarkic N, López JH, Antunes WDT, Pereira MFC, Matos APAD, Santos AL. A possible Echinococcus granulosus calcified cyst found in a medieval adult female from the churchyard of Santo Domingo de Silos (Prádena del Rincón, Madrid, Spain). INTERNATIONAL JOURNAL OF PALEOPATHOLOGY 2017; 16:5-13. [PMID: 28290311 DOI: 10.1016/j.ijpp.2017.01.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 01/16/2017] [Accepted: 01/16/2017] [Indexed: 06/06/2023]
Abstract
Calcification, or mineralisation, can occur as part of a natural process, or by pathological processes. The purpose of this work is to examine an unidentified semi-spherical and perforate hollow mass, found near the pelvis of an adult female, dated 12th-13th century AD, exhumed of the Church of Santo Domingo de Silos (Prádena del Ricón, Madrid, Spain). The mass was examined by SEM and Energy Dispersive X-Ray Spectroscopy. These procedures revealed a heterogeneous inner surface with both smooth and irregular areas. A larger spherical and several smaller crescent-shaped perforations were noticed. X-ray microanalysis revealed the presence of the elements C, K, P, Ca, Al, Si, Fe, and Mg. The co-localisation of Ca and P suggests that they may be combined in a mineral matrix, likely formed in vivo. Other minerals probably came from the soil, although Fe could be related to the presence of blood. The macroscopic and microscopic appearances, chemical composition, and location of the calcified mass point to a possible hydatid cyst from Echinococcus granulosus, common in agricultural populations. This study used a suite of analytical techniques that are useful in the diagnosis of unknown calcified masses and can, therefore, be recommended for use in future analytical work.
Collapse
Affiliation(s)
- Álvaro M Monge Calleja
- Centro de Investigação em Antropologia e Saúde (CIAS), Department of Life Sciences, University of Coimbra, Portugal.
| | - Natasa Sarkic
- Depart. Biología, Unidad Antropología Física, Universidad Autónoma de Madrid, Spain
| | - Jesus Herrerín López
- Depart. Biología, Unidad Antropología Física, Universidad Autónoma de Madrid, Spain
| | - Wilson D T Antunes
- Laboratório de Defesa Biológica, Unidade Militar Laboratorial de Defesa Biológica e Química, Exército, Portugal
| | | | - António Pedro Alves de Matos
- CiiEM, Egas Moniz Interdisciplinary Research Center, University Campus of Quinta da Granja, Monte de Caparica, Portugal
| | - Ana Luísa Santos
- Centro de Investigação em Antropologia e Saúde (CIAS), Department of Life Sciences, University of Coimbra, Portugal
| |
Collapse
|
|
24
|
Functions of Rho family of small GTPases and Rho-associated coiled-coil kinases in bone cells during differentiation and mineralization. Biochim Biophys Acta Gen Subj 2017; 1861:1009-1023. [PMID: 28188861 DOI: 10.1016/j.bbagen.2017.02.005] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Revised: 02/02/2017] [Accepted: 02/06/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Members of Rho-associated coiled-coil kinases (ROCKs) are effectors of Rho family of small GTPases. ROCKs have multiple functions that include regulation of cellular contraction and polarity, adhesion, motility, proliferation, apoptosis, differentiation, maturation and remodeling of the extracellular matrix (ECM). SCOPE OF THE REVIEW Here, we focus on the action of RhoA and RhoA effectors, ROCK1 and ROCK2, in cells related to tissue mineralization: mesenchymal stem cells, chondrocytes, preosteoblasts, osteoblasts, osteocytes, lining cells and osteoclasts. MAJOR CONCLUSIONS The activation of the RhoA/ROCK pathway promotes stress fiber formation and reduces chondrocyte and osteogenic differentiations, in contrast to that in mesenchymal stem cells which stimulated the osteogenic and the chondrogenic differentiation. The effects of Rac1 and Cdc42 in promoting chondrocyte hypertrophy and of Rac1, Rac2 and Cdc42 in osteoclast are discussed. In addition, members of the Rho family of GTPases such Rac1, Rac2, Rac3 and Cdc42, acting upstream of ROCK and/or other protein effectors, may compensate the actions of RhoA, affecting directly or indirectly the actions of ROCKs as well as other protein effectors. GENERAL SIGNIFICANCE ROCK activity can trigger cartilage degradation and affect bone formation, therefore these kinases may represent a possible therapeutic target to treat osteoarthritis and osseous diseases. Inhibition of Rho/ROCK activity in chondrocytes prevents cartilage degradation, stimulate mineralization of osteoblasts and facilitate bone formation around implanted metals. Treatment with osteoprotegerin results in a significant decrease in the expression of Rho GTPases, ROCK1 and ROCK2, reducing bone resorption. Inhibition of ROCK signaling increases osteoblast differentiation in a topography-dependent manner.
Collapse
|
|
25
|
Schauer KL, LeMoine CMR, Pelin A, Corradi N, Warren WC, Grosell M, McDonald MD. A proteinaceous organic matrix regulates carbonate mineral production in the marine teleost intestine. Sci Rep 2016; 6:34494. [PMID: 27694946 PMCID: PMC5046086 DOI: 10.1038/srep34494] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Accepted: 09/14/2016] [Indexed: 12/24/2022] Open
Abstract
Marine teleost fish produce CaCO3 in their intestine as part of their osmoregulatory strategy. This precipitation is critical for rehydration and survival of the largest vertebrate group on earth, yet the molecular mechanisms that regulate this reaction are unknown. Here, we isolate and characterize an organic matrix associated with the intestinal precipitates produced by Gulf toadfish (Opsanus beta). Toadfish precipitates were purified using two different methods, and the associated organic matrix was extracted. Greater than 150 proteins were identified in the isolated matrix by mass spectrometry and subsequent database searching using an O. beta transcriptomic sequence library produced here. Many of the identified proteins were enriched in the matrix compared to the intestinal fluid, and three showed no substantial homology to any previously characterized protein in the NCBI database. To test the functionality of the isolated matrix, a micro-modified in vitro calcification assay was designed, which revealed that low concentrations of isolated matrix substantially promoted CaCO3 production, where high concentrations showed an inhibitory effect. High concentrations of matrix also decreased the incorporation of magnesium into the forming mineral, potentially providing an explanation for the variability in magnesium content observed in precipitates produced by different fish species.
Collapse
Affiliation(s)
- Kevin L Schauer
- Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Science, University of Miami, Miami, FL, 33149, USA
| | - Christophe M R LeMoine
- Department of Biology, Brandon University, Brandon, MB, R7A 6A9, Canada.,Canadian Institute for Advanced Research, Department of Biology, University of Ottawa, Ottawa, ON, K1N 6N5, Canada
| | - Adrian Pelin
- Canadian Institute for Advanced Research, Department of Biology, University of Ottawa, Ottawa, ON, K1N 6N5, Canada
| | - Nicolas Corradi
- Canadian Institute for Advanced Research, Department of Biology, University of Ottawa, Ottawa, ON, K1N 6N5, Canada
| | - Wesley C Warren
- McDonnell Genome Institute, Washington University School of Medicine, St Louis, Missouri 63108, USA
| | - Martin Grosell
- Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Science, University of Miami, Miami, FL, 33149, USA
| | | |
Collapse
|
|
26
|
Witzmann FA, Evan AP, Coe FL, Worcester EM, Lingeman JE, Williams JC. Label-free proteomic methodology for the analysis of human kidney stone matrix composition. Proteome Sci 2016; 14:4. [PMID: 26924944 PMCID: PMC4769560 DOI: 10.1186/s12953-016-0093-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 02/19/2016] [Indexed: 11/10/2022] Open
Abstract
Background Kidney stone matrix protein composition is an important yet poorly understood aspect of nephrolithiasis. We hypothesized that this proteome is considerably more complex than previous reports have indicated and that comprehensive proteomic profiling of the kidney stone matrix may demonstrate relevant constitutive differences between stones. We have analyzed the matrices of two unique human calcium oxalate stones (CaOx-Ia and CaOx-Id) using a simple but effective chaotropic reducing solution for extraction/solubilization combined with label-free quantitative mass spectrometry to generate a comprehensive profile of their proteomes, including physicochemical and bioinformatic analysis.` Results We identified and quantified 1,059 unique protein database entries in the two human kidney stone samples, revealing a more complex proteome than previously reported. Protein composition reflects a common range of proteins related to immune response, inflammation, injury, and tissue repair, along with a more diverse set of proteins unique to each stone. Conclusion The use of a simple chaotropic reducing solution and moderate sonication for extraction and solubilization of kidney stone powders combined with label-free quantitative mass spectrometry has yielded the most comprehensive list to date of the proteins that constitute the human kidney stone proteome. Electronic supplementary material The online version of this article (doi:10.1186/s12953-016-0093-x) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Frank A Witzmann
- Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Room 362A, Indianapolis, IN 46202-5120 USA
| | - Andrew P Evan
- Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN USA
| | - Fredric L Coe
- Department of Medicine, Nephrology Section, University of Chicago, Chicago, IL USA
| | - Elaine M Worcester
- Department of Medicine, Nephrology Section, University of Chicago, Chicago, IL USA
| | - James E Lingeman
- International Kidney Stone Institute, Methodist Hospital, Indianapolis, IN USA
| | - James C Williams
- Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN USA
| |
Collapse
|
|
27
|
Abstract
A hallmark of aging, and major contributor to the increased prevalence of cardiovascular disease in patients with chronic kidney disease (CKD), is the progressive structural and functional deterioration of the arteries and concomitant accrual of mineral. Vascular calcification (VC) was long viewed as a degenerative age-related pathology that resulted from the passive deposition of mineral in the extracellular matrix; however, since the discovery of "bone-related" protein expression in calcified atherosclerotic plaques over 20 years ago, a plethora of studies have evoked the now widely accepted view that VC is a highly regulated and principally cell-mediated phenomenon that recapitulates many features of physiologic ossification. Central to this theory are changes in vascular smooth muscle cell (VSMC) phenotype and viability, thought to be driven by chronic exposure to a number of dystrophic stimuli characteristics of the uremic state. Here, dedifferentiated synthetic VSMCs are seen to spawn calcifying matrix vesicles that actively seed mineralization of the arterial matrix. This review provides an overview of the major epidemiological, histological, and molecular aspects of VC in the context of CKD, and a counterpoint to the prevailing paradigm that emphasizes the primacy of VSMC-mediated mechanisms. Particular focus is given to the import of protein and small molecule inhibitors in regulating physiologic and pathological mineralization and the emerging role of mineral nanoparticles and their interplay with proinflammatory processes.
Collapse
Affiliation(s)
- Edward R Smith
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.
| |
Collapse
|
|
28
|
Boraldi F, Bartolomeo A, Di Bari C, Cocconi A, Quaglino D. Donor's age and replicative senescence favour the in-vitro mineralization potential of human fibroblasts. Exp Gerontol 2015; 72:218-26. [PMID: 26494600 DOI: 10.1016/j.exger.2015.10.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Revised: 10/16/2015] [Accepted: 10/19/2015] [Indexed: 11/30/2022]
Abstract
Aberrant mineralization of soft connective tissues (ectopic calcification) may occur as a frequent age-related complication. Still, it remains unclear the role of mesenchymal cell donor's age and of replicative senescence on ectopic calcification. Therefore, the ability of cells to deposit in-vitro hydroxyapatite crystals and the expression of progressive ankylosis protein homolog (ANKH), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), tissue non specific alkaline phosphatase (TNAP) and osteopontin (OPN) have been evaluated in human dermal fibroblasts derived from neonatal (nHDF) and adult (aHDF) donors (ex-vivo ageing model) or at low and high cumulative population doublings (CPD) up to replicative senescence (in-vitro ageing model). This study demonstrates that: 1) replicative senescence favours hydroxyapatite formation in cultured fibroblasts; 2) donor's age acts as a major modulator of the mineralizing potential of HDF, since nHDF are less prone than aHDF to induce calcification; 3) donor's age and replicative senescence play in concert synergistically increasing the calcification process; 4) the ANKH+ENPP1/TNAP ratio, being crucial for pyrophosphate/inorganic phosphate balance, is greatly influenced by donor's age, as well as by replicative senescence, and regulates mineral deposition; 5) OPN is only modulated by replicative senescence.
Collapse
Affiliation(s)
- Federica Boraldi
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Angelica Bartolomeo
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Caterina Di Bari
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Andrea Cocconi
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Daniela Quaglino
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
| |
Collapse
|
|
29
|
Levine MA. Pathological calcification and the mystery of Lot's wife. Cell Cycle 2015; 14:3354-5. [PMID: 26375426 DOI: 10.1080/15384101.2015.1093815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Affiliation(s)
- Michael A Levine
- a Division of Endocrinology and Diabetes; The Children's Hospital of Philadelphia and Department of Pediatrics; University of Pennsylvania Perelman School of Medicine ; Philadelphia , PA USA
| |
Collapse
|
|
30
|
Bolean M, Simão AMS, Kiffer-Moreira T, Hoylaerts MF, Millán JL, Itri R, Ciancaglini P. Proteoliposomes with the ability to transport Ca(2+) into the vesicles and hydrolyze phosphosubstrates on their surface. Arch Biochem Biophys 2015; 584:79-89. [PMID: 26325078 DOI: 10.1016/j.abb.2015.08.018] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Revised: 08/26/2015] [Accepted: 08/27/2015] [Indexed: 11/19/2022]
Abstract
We describe the production of stable DPPC and DPPC:DPPS-proteoliposomes harboring annexin V (AnxA5) and tissue-nonspecific alkaline phosphatase (TNAP) and their use to investigate whether the presence of AnxA5 impacts the kinetic parameters for hydrolysis of TNAP substrates at physiological pH. The best catalytic efficiency was achieved in DPPS 10%-proteoliposomes (molar ratio), conditions that also increased the specificity of TNAP hydrolysis of PPi. Melting behavior of liposomes and proteoliposomes was analyzed via differential scanning calorimetry. The presence of 10% DPPS in DPPC-liposomes causes a broadening of the transition peaks, with AnxA5 and TNAP promoting a decrease in ΔH values. AnxA5 was able to mediate Ca(2+)-influx into the DPPC and DPPC:DPPS 10%-vesicles at physiological Ca(2+) concentrations (∼2 mM). This process was not affected by the presence of TNAP in the proteoliposomes. However, AnxA5 significantly affects the hydrolysis of TNAP substrates. Studies with GUVs confirmed the functional reconstitution of AnxA5 in the mimetic systems. These proteoliposomes are useful as mimetics of mineralizing cell-derived matrix vesicles, known to be responsible for the initiation of endochondral ossification, as they successfully transport Ca(2+) and possess the ability to hydrolyze phosphosubstrates in the lipid-water interface.
Collapse
Affiliation(s)
- Maytê Bolean
- Depto. Química, FFCLRP-USP, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
| | - Ana Maria S Simão
- Depto. Química, FFCLRP-USP, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
| | - Tina Kiffer-Moreira
- Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
| | - Marc F Hoylaerts
- Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
| | - José Luis Millán
- Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
| | - Rosangela Itri
- Depto. Física Aplicada, Instituto de Física, IF-USP, São Paulo, SP, Brazil
| | - Pietro Ciancaglini
- Depto. Química, FFCLRP-USP, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
| |
Collapse
|
|
31
|
Vilder EYGD, Vanakker OM. From variome to phenome: Pathogenesis, diagnosis and management of ectopic mineralization disorders. World J Clin Cases 2015; 3:556-574. [PMID: 26244149 PMCID: PMC4517332 DOI: 10.12998/wjcc.v3.i7.556] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 02/27/2015] [Accepted: 05/18/2015] [Indexed: 02/05/2023] Open
Abstract
Ectopic mineralization - inappropriate biomineralization in soft tissues - is a frequent finding in physiological aging processes and several common disorders, which can be associated with significant morbidity and mortality. Further, pathologic mineralization is seen in several rare genetic disorders, which often present life-threatening phenotypes. These disorders are classified based on the mechanisms through which the mineralization occurs: metastatic or dystrophic calcification or ectopic ossification. Underlying mechanisms have been extensively studied, which resulted in several hypotheses regarding the etiology of mineralization in the extracellular matrix of soft tissue. These hypotheses include intracellular and extracellular mechanisms, such as the formation of matrix vesicles, aberrant osteogenic and chondrogenic signaling, apoptosis and oxidative stress. Though coherence between the different findings is not always clear, current insights have led to improvement of the diagnosis and management of ectopic mineralization patients, thus translating pathogenetic knowledge (variome) to the phenotype (phenome). In this review, we will focus on the clinical presentation, pathogenesis and management of primary genetic soft tissue mineralization disorders. As examples of dystrophic calcification disorders Pseudoxanthoma elasticum, Generalized arterial calcification of infancy, Keutel syndrome, Idiopathic basal ganglia calcification and Arterial calcification due to CD73 (NT5E) deficiency will be discussed. Hyperphosphatemic familial tumoral calcinosis will be reviewed as an example of mineralization disorders caused by metastatic calcification.
Collapse
|
|
32
|
Inagaki Y, Kashima TG, Hookway ES, Tanaka Y, Hassan AB, Oppermann U, Athanasou NA. Dentine matrix protein 1 (DMP-1) is a marker of bone formation and mineralisation in soft tissue tumours. Virchows Arch 2015; 466:445-52. [DOI: 10.1007/s00428-014-1706-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Revised: 11/15/2014] [Accepted: 12/02/2014] [Indexed: 01/29/2023]
|
|
33
|
Apschner A, Huitema LFA, Ponsioen B, Peterson-Maduro J, Schulte-Merker S. Zebrafish enpp1 mutants exhibit pathological mineralization, mimicking features of generalized arterial calcification of infancy (GACI) and pseudoxanthoma elasticum (PXE). Dis Model Mech 2014; 7:811-22. [PMID: 24906371 PMCID: PMC4073271 DOI: 10.1242/dmm.015693] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In recent years it has become clear that, mechanistically, biomineralization is a process that has to be actively inhibited as a default state. This inhibition must be released in a rigidly controlled manner in order for mineralization to occur in skeletal elements and teeth. A central aspect of this concept is the tightly controlled balance between phosphate, a constituent of the biomineral hydroxyapatite, and pyrophosphate, a physiochemical inhibitor of mineralization. Here, we provide a detailed analysis of a zebrafish mutant, dragonfish (dgf), which is mutant for ectonucleoside pyrophosphatase/phosphodiesterase 1 (Enpp1), a protein that is crucial for supplying extracellular pyrophosphate. Generalized arterial calcification of infancy (GACI) is a fatal human disease, and the majority of cases are thought to be caused by mutations in ENPP1. Furthermore, some cases of pseudoxanthoma elasticum (PXE) have recently been linked to ENPP1. Similar to humans, we show here that zebrafish enpp1 mutants can develop ectopic calcifications in a variety of soft tissues - most notably in the skin, cartilage elements, the heart, intracranial space and the notochord sheet. Using transgenic reporter lines, we demonstrate that ectopic mineralizations in these tissues occur independently of the expression of typical osteoblast or cartilage markers. Intriguingly, we detect cells expressing the osteoclast markers Trap and CathepsinK at sites of ectopic calcification at time points when osteoclasts are not yet present in wild-type siblings. Treatment with the bisphosphonate etidronate rescues aspects of the dgf phenotype, and we detected deregulated expression of genes that are involved in phosphate homeostasis and mineralization, such as fgf23, npt2a, entpd5 and spp1 (also known as osteopontin). Employing a UAS-GalFF approach, we show that forced expression of enpp1 in blood vessels or the floorplate of mutant embryos is sufficient to rescue the notochord mineralization phenotype. This indicates that enpp1 can exert its function in tissues that are remote from its site of expression.
Collapse
Affiliation(s)
- Alexander Apschner
- Hubrecht Institute - KNAW & UMC Utrecht, 3548CT Utrecht, The Netherlands
| | - Leonie F A Huitema
- Hubrecht Institute - KNAW & UMC Utrecht, 3548CT Utrecht, The Netherlands
| | - Bas Ponsioen
- Hubrecht Institute - KNAW & UMC Utrecht, 3548CT Utrecht, The Netherlands
| | | | - Stefan Schulte-Merker
- Hubrecht Institute - KNAW & UMC Utrecht, 3548CT Utrecht, The Netherlands. WUR, Experimental Zoology, 3700AH Wageningen, The Netherlands. Institute of Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, University of Münster, 48149 Münster, Germany.
| |
Collapse
|
|
34
|
Diagnosis and Clinical Manifestations of Calcium Pyrophosphate and Basic Calcium Phosphate Crystal Deposition Diseases. Rheum Dis Clin North Am 2014; 40:207-29. [DOI: 10.1016/j.rdc.2014.01.011] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
|
|
35
|
Abstract
Calcinosis cutis (CC) is a type of calcinosis wherein insoluble compounds or salts deposited on the skin. Clinical diagnosis of CC is usually achieved through time consuming histopathological or immunohistochemical procedures, but it can only be empirically identified by experienced practitioners. The use of advanced vibrational spectroscopy has been recently shown to have great potential as a diagnostic technique for various diseased tissues because it analyses the chemical composition of diseased tissue rather than its anatomy and predicts disease progression. This review article includes a summary of the application of Fourier transform infrared (FT-IR) and Raman spectroscopic or microspectroscopic analysis for the rapid diagnosis and identification of the chemical composition of skin calcified deposits in patients with various CC symptoms. Both advanced techniques not only can detect the types of insoluble salts such as calcium phosphate, calcium carbonate, and monosodium urate, and β-carotene in the calcified deposits of human skin tissue but also can directly differentiate the carbonate substitution in the apatite structure of the skin calcified deposits. In particular, the combination of both vibrational techniques may provide complementary information to simultaneously assess the intact components of the calcified deposits. In the future, both FT-IR and Raman vibrational microspectroscopic techniques will become available tools to support the standard test techniques currently used in some clinical diagnoses. Molecular spectroscopy technique is rapidly changing disease diagnosis and management.
Collapse
|
|
36
|
Dorvee JR, Veis A. Water in the formation of biogenic minerals: peeling away the hydration layers. J Struct Biol 2013; 183:278-303. [PMID: 23791831 DOI: 10.1016/j.jsb.2013.06.007] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Revised: 05/14/2013] [Accepted: 06/09/2013] [Indexed: 12/31/2022]
Abstract
Minerals of biogenic origin form and crystallize from aqueous environments at ambient temperatures and pressures. The in vivo environment either intracellular or intercellular, contains many components that modulate both the activity of the ions which associate to form the mineral, as well as the activity and structure of the crowded water. Most of the studies about the mechanism of mineralization, that is, the detailed pathways by which the mineral ions proceed from solution to crystal state, have been carried out in relatively dilute solutions and clean solutions. These studies have considered both thermodynamic and kinetic controls. Most have not considered the water itself. Is the water a passive bystander, or is it intimately a participant in the mineral ion densification reaction? A wide range of experiments show that the mineralization pathways proceed through a series of densification stages with intermediates, such as a "dense liquid" phase and the prenucleation clusters that form within it. This is in contrast to the idea of a single step phase transition, but consistent with the Gibbs concept of discontinuous phase transitions from supersaturated mother liquor to crystal. Further changes in the water structure at every surface and interface during densification guides the free energy trajectory leading to the crystalline state. In vertebrates, mineralization takes place in a hydrated collagen matrix, thus water must be considered as a direct participant. Although different in detail, the crystallization of calcium phosphates, as apatite, and calcium carbonates, as calcite, are mechanistically identical from the viewpoint of water.
Collapse
Affiliation(s)
- Jason R Dorvee
- Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA
| | | |
Collapse
|
|
37
|
Cox RF, Morgan MP. Microcalcifications in breast cancer: Lessons from physiological mineralization. Bone 2013; 53:437-50. [PMID: 23334083 DOI: 10.1016/j.bone.2013.01.013] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2012] [Revised: 01/07/2013] [Accepted: 01/08/2013] [Indexed: 02/02/2023]
Abstract
Mammographic mammary microcalcifications are routinely used for the early detection of breast cancer, however the mechanisms by which they form remain unclear. Two species of mammary microcalcifications have been identified; calcium oxalate and hydroxyapatite. Calcium oxalate is mostly associated with benign lesions of the breast, whereas hydroxyapatite is associated with both benign and malignant tumors. The way in which hydroxyapatite forms within mammary tissue remains largely unexplored, however lessons can be learned from the process of physiological mineralization. Normal physiological mineralization by osteoblasts results in hydroxyapatite deposition in bone. This review brings together existing knowledge from the field of physiological mineralization and juxtaposes it with our current understanding of the genesis of mammary microcalcifications. As an increasing number of breast cancers are being detected in their non-palpable stage through mammographic microcalcifications, it is important that future studies investigate the underlying mechanisms of their formation in order to fully understand the significance of this unique early marker of breast cancer.
Collapse
Affiliation(s)
- Rachel F Cox
- Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland
| | | |
Collapse
|