José Luís Millán
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View article: <i>Alpl</i> Ablation in Dental Epithelium Disrupts Ameloblasts and Incisor Enamel Mineralization in Male Mice
<i>Alpl</i> Ablation in Dental Epithelium Disrupts Ameloblasts and Incisor Enamel Mineralization in Male Mice Open
Tissue-nonspecific alkaline phosphatase (Gene: ALPL; protein: TNAP) is a mineralization-associated enzyme that catalyzes several physiological substrates and is widely expressed in skeletal and non-skeletal tissues indicating diverse physi…
View article: TNAP dephosphorylates phosphocholine and phosphoethanolamine and participates in triglyceride transport from the liver to the bloodstream
TNAP dephosphorylates phosphocholine and phosphoethanolamine and participates in triglyceride transport from the liver to the bloodstream Open
Tissue-nonspecific alkaline phosphatase (TNAP) is primarily known for its role in skeletal mineralization, through the hydrolysis of inorganic pyrophosphate (PPi). Here we demonstrate that TNAP-knockout mice exhibit liver steato…
View article: Genetic reduction or deletion of osteopontin in osteomalacic <i>Hyp</i> mice fails to ameliorate dentoalveolar defects
Genetic reduction or deletion of osteopontin in osteomalacic <i>Hyp</i> mice fails to ameliorate dentoalveolar defects Open
X-linked hypophosphatemia (XLH) is caused by inactivating mutations in PHEX, leading to disturbed mineral metabolism, rickets, and osteomalacia. Dentoalveolar defects affecting dentin, cementum, and alveolar bone, contribute to dental absc…
View article: Proof-of-principle for enhanced dentoalveolar mineralization using exogenous tissue-nonspecific alkaline phosphatase in the <i>Hyp</i> mouse model of X-linked hypophosphatemia
Proof-of-principle for enhanced dentoalveolar mineralization using exogenous tissue-nonspecific alkaline phosphatase in the <i>Hyp</i> mouse model of X-linked hypophosphatemia Open
X-linked hypophosphatemia (XLH) is caused by mutations in the PHEX gene, which leads to increased levels of fibroblast growth factor 23 and hypophosphatemia, contributing to rickets, osteomalacia, and dentoalveolar defects, including sever…
View article: Hypophosphatasia—pathophysiological understanding, preclinical data looking beyond the skeleton, and upcoming treatments
Hypophosphatasia—pathophysiological understanding, preclinical data looking beyond the skeleton, and upcoming treatments Open
Hypophosphatasia (HPP) is a genetic disorder caused by loss-of-function mutations in the ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP), an enzyme essential for physiological skeletal/dental mineralization. In HPP, T…
View article: ENPP1 inhibition as a therapeutic approach for later-onset hypophosphatasia
ENPP1 inhibition as a therapeutic approach for later-onset hypophosphatasia Open
Hypophosphatasia (HPP) is caused by loss-of-function mutations in the human ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP), whose deficiency results in the accumulation of the calcification inhibitor inorganic pyroph…
View article: Distinct bone metabolic networks identified in Phospho1−/− mice vs. wild type mice using [18F]FDG total-body PET
Distinct bone metabolic networks identified in Phospho1−/− mice vs. wild type mice using [18F]FDG total-body PET Open
Introduction Total-body PET is a recent development in clinical imaging that produces large datasets involving multiple tissues, enabling the use of new analytical methods for multi-organ assessments, such as network analysis—a well-develo…
View article: Dentoalveolar defects and impaired alveolar bone healing in a neural crest directed conditional knockout mouse model of hypophosphatasia
Dentoalveolar defects and impaired alveolar bone healing in a neural crest directed conditional knockout mouse model of hypophosphatasia Open
Hypophosphatasia (HPP) is an inherited error-of-metabolism caused by loss-of-function mutations in ALPL-encoded tissue-nonspecific alkaline phosphatase (TNAP). HPP has wide-ranging severity, including a clinical subtype called odontohypoph…
View article: Early-stage therapeutic efficacy of TNAP inhibition using a novel milder murine model of CKD-MBD
Early-stage therapeutic efficacy of TNAP inhibition using a novel milder murine model of CKD-MBD Open
Chronic kidney disease (CKD) is a complicated systemic disease displaying various pathophysiological symptoms including mineral bone disorder (CKD-MBD). Ideally, early intervention for CKD-MBD would be desirable, however, there is not enou…
View article: A protein corona modulates the function of mineralization-competent matrix vesicles
A protein corona modulates the function of mineralization-competent matrix vesicles Open
Mineralizing cells release a special class of extracellular vesicles known as matrix vesicles (MV), crucial for bone mineralization. Following their release, MV anchor to the extracellular matrix (ECM), where their highly specialized enzym…
View article: Correction: Zinc-alkaline phosphatase at sites of aortic calcification
Correction: Zinc-alkaline phosphatase at sites of aortic calcification Open
View article: Zinc-alkaline phosphatase at sites of aortic calcification
Zinc-alkaline phosphatase at sites of aortic calcification Open
View article: Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts
Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts Open
Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate and ATP to provide inorgan…
View article: The biochemistry of mineralizing extracellular vesicles. Part I: The role of phosphatases
The biochemistry of mineralizing extracellular vesicles. Part I: The role of phosphatases Open
View article: Do Media Extracellular Vesicles and Extracellular Vesicles Bound to the Extracellular Matrix Represent Distinct Types of Vesicles?
Do Media Extracellular Vesicles and Extracellular Vesicles Bound to the Extracellular Matrix Represent Distinct Types of Vesicles? Open
Mineralization-competent cells, including hypertrophic chondrocytes, mature osteoblasts, and osteogenic-differentiated smooth muscle cells secrete media extracellular vesicles (media vesicles) and extracellular vesicles bound to the extrac…
View article: Annexin A5 stabilizes matrix vesicle-biomimetic lipid membranes: unravelling a new role of annexins in calcification
Annexin A5 stabilizes matrix vesicle-biomimetic lipid membranes: unravelling a new role of annexins in calcification Open
Matrix vesicles are a special class of extracellular vesicles thought to actively contribute to both physiologic and pathologic mineralization. Proteomic studies have shown that matrix vesicles possess high amounts of annexin A5, suggestin…
View article: Evidence that pyrophosphate acts as an extracellular signalling molecule to exert direct functional effects in primary cultures of osteoblasts and osteoclasts
Evidence that pyrophosphate acts as an extracellular signalling molecule to exert direct functional effects in primary cultures of osteoblasts and osteoclasts Open
View article: Dentoalveolar Alterations in an <scp>Adenine‐Induced</scp> Chronic Kidney Disease Mouse Model
Dentoalveolar Alterations in an <span>Adenine‐Induced</span> Chronic Kidney Disease Mouse Model Open
Chronic kidney disease (CKD) is characterized by kidney damage and loss of renal function. CKD mineral and bone disorder (CKD–MBD) describes the dysregulation of mineral homeostasis, including hyperphosphatemia and elevated parathyroid hor…
View article: Increased PHOSPHO1 and alkaline phosphatase expression during the anabolic bone response to intermittent parathyroid hormone delivery
Increased PHOSPHO1 and alkaline phosphatase expression during the anabolic bone response to intermittent parathyroid hormone delivery Open
The administration of intermittent parathyroid hormone (iPTH) is anabolic to the skeleton. Recent studies with cultured osteoblasts have revealed that the expression of PHOSPHO1, a bone‐specific phosphatase essential for the initiation of …
View article: Gene Therapy Using Recombinant <scp>AAV</scp> Type 8 Vector Encoding <scp>TNAP‐D<sub>10</sub></scp> Improves the Skeletal Phenotypes in Murine Models of Osteomalacia
Gene Therapy Using Recombinant <span>AAV</span> Type 8 Vector Encoding <span>TNAP‐D<sub>10</sub></span> Improves the Skeletal Phenotypes in Murine Models of Osteomalacia Open
Hypophosphatasia (HPP), caused by loss‐of‐function mutations in the ALPL gene encoding tissue‐nonspecific alkaline phosphatase (TNAP), is characterized by skeletal and dental hypomineralization that can vary in severity from life‐threateni…
View article: Shedding Light on the Role of Na,K-ATPase as a Phosphatase during Matrix-Vesicle-Mediated Mineralization
Shedding Light on the Role of Na,K-ATPase as a Phosphatase during Matrix-Vesicle-Mediated Mineralization Open
Matrix vesicles (MVs) contain the whole machinery necessary to initiate apatite formation in their lumen. We suspected that, in addition to tissue-nonspecific alkaline phosphatase (TNAP), Na,K,-ATPase (NKA) could be involved in supplying p…
View article: Mineralization Profile of Annexin A6-Harbouring Proteoliposomes: Shedding Light on the Role of Annexin A6 on Matrix Vesicle-Mediated Mineralization
Mineralization Profile of Annexin A6-Harbouring Proteoliposomes: Shedding Light on the Role of Annexin A6 on Matrix Vesicle-Mediated Mineralization Open
The biochemical machinery involved in matrix vesicles-mediated bone mineralization involves a specific set of lipids, enzymes, and proteins. Annexins, among their many functions, have been described as responsible for the formation and sta…
View article: Increased PHOSPHO1 expression mediates cortical bone mineral density in renal osteodystrophy
Increased PHOSPHO1 expression mediates cortical bone mineral density in renal osteodystrophy Open
Patients with advanced chronic kidney disease (CKD) often present with skeletal abnormalities, a condition known as renal osteodystrophy (ROD). While tissue non-specific alkaline phosphatase (TNAP) and PHOSPHO1 are critical for bone minera…
View article: NPP1 and TNAP hydrolyze ATP synergistically during biomineralization
NPP1 and TNAP hydrolyze ATP synergistically during biomineralization Open
View article: Ultrasensitive Diamond Microelectrode Application in the Detection of Ca2+ Transport by AnnexinA5-Containing Nanostructured Liposomes
Ultrasensitive Diamond Microelectrode Application in the Detection of Ca2+ Transport by AnnexinA5-Containing Nanostructured Liposomes Open
This report describes the innovative application of high sensitivity Boron-doped nanocrystalline diamond microelectrodes for tracking small changes in Ca2+ concentration due to binding to Annexin-A5 inserted into the lipid bilayer of lipos…
View article: Inhibition of alkaline phosphatase impairs dyslipidemia and protects mice from atherosclerosis
Inhibition of alkaline phosphatase impairs dyslipidemia and protects mice from atherosclerosis Open
View article: Fluorescence evidence of annexin A6 translocation across membrane in model matrix vesicles during apatite formation
Fluorescence evidence of annexin A6 translocation across membrane in model matrix vesicles during apatite formation Open
Matrix vesicles (MVs) are 100–300 nm spherical structures released by mineralization competent cells to initiate formation of apatite, the mineral component in bones. Among proteins present in MVs, annexin A6 (AnxA6) is thought to be ubiqu…
View article: Perspective on Dentoalveolar Manifestations Resulting From PHOSPHO1 Loss-of-Function: A Form of Pseudohypophosphatasia?
Perspective on Dentoalveolar Manifestations Resulting From PHOSPHO1 Loss-of-Function: A Form of Pseudohypophosphatasia? Open
Mineralization of the skeleton occurs by several physicochemical and biochemical processes and mechanisms that facilitate the deposition of hydroxyapatite (HA) in specific areas of the extracellular matrix (ECM). Two key phosphatases, phos…
View article: TNAP upregulation is a critical factor in Tauopathies and its blockade ameliorates neurotoxicity and increases life-expectancy
TNAP upregulation is a critical factor in Tauopathies and its blockade ameliorates neurotoxicity and increases life-expectancy Open
View article: The functional role of soluble proteins acquired by extracellular vesicles
The functional role of soluble proteins acquired by extracellular vesicles Open
Extracellular vesicles (EVs) are lipid bilayer‐enclosed nanosized particles released by all cell types during physiological as well as pathophysiological processes to carry out diverse biological functions, including acting as sources of c…