Publications by authors named "Somerman M"

Background: Mineral metabolism is critical for proper development of hard tissues of the skeleton and dentition. The dentoalveolar complex includes the following 4 mineralized tissues: enamel, dentin, cementum, and alveolar bone. Developmental processes of these tissues are affected by inherited disorders that disrupt phosphate and pyrophosphate homeostasis, although manifestations are distinct from those in the skeleton.

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Background: Fibroblast growth factor receptor-3 (FGFR3) gain-of-function mutations are linked to achondroplasia. Infigratinib, a FGFR1-3 tyrosine kinase inhibitor, improves skeletal growth in an achondroplasia mouse model. FGFs and their receptors have critical roles in developing teeth, yet effects of infigratinib on tooth development have not been assessed.

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Citrate is a critical metabolic substrate and key regulator of energy metabolism in mammalian cells. It has been known for decades that the skeleton contains most (>85%) of the body's citrate, but the question of why and how this metabolite should be partitioned in bone has received singularly little attention. Here, we show that osteoblasts use a specialized metabolic pathway to regulate uptake, endogenous production, and the deposition of citrate into bone.

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Biallelic ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency induces vascular/soft tissue calcifications in generalized arterial calcification of infancy (GACI), and low bone mass with phosphate-wasting rickets in GACI survivors (autosomal hypophosphatemic rickets type-2). ENPP1 haploinsufficiency induces early-onset osteoporosis and mild phosphate wasting in adults. Both conditions demonstrate the unusual combination of reduced accrual of skeletal mineral, yet excess and progressive heterotopic mineralization.

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Bone sialoprotein (gene: ; protein: BSP) is a multifunctional extracellular matrix protein present in bone, cementum, and dentin. Accumulating evidence supports BSP as a key regulator of mineralized tissue formation via evolutionarily conserved functional domains, including a C-terminal integrin-binding Arg-Gly-Asp (RGD) domain implicated in extracellular matrix-cell signaling. Ablation of in mice () results in impaired bone growth and mineralization and defective osteoclastogenesis, with effects in the craniofacial region including reduced acellular cementum formation, detachment of the periodontal ligament (PDL), alveolar bone hypomineralization, and severe periodontal breakdown.

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The goal of this perspective article is to use multiple idiopathic cervical root resorption (MICRR) as a model to demonstrate the need for transdisciplinary collaborations, from basic science to treatment planning, to improve the quality of health care for all. This is not a review of the literature on the current state of MICRR. Tooth root resorption is a normal physiological process required for resorption and exfoliation of primary teeth; however, root resorption of adult teeth is largely pathological.

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Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder caused by mutations in , , , or FGF23 autoantibodies. Prominent features include high blood phosphate and calcific masses, usually adjacent to large joints. Dental defects have been reported, but not systematically described.

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Factors regulating the ratio of pyrophosphate (PP) to phosphate (P) modulate biomineralization. Tissue-nonspecific alkaline phosphatase (TNAP) is a key promineralization enzyme that hydrolyzes the potent mineralization inhibitor PP. The goal of this study was to determine whether TNAP could promote periodontal regeneration in bone sialoprotein knockout mice ( mice), which are known to have a periodontal disease phenotype.

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Micro-computed tomography (μCT) has become essential for analysis of mineralized as well as nonmineralized tissues and is therefore widely applicable in the life sciences. However, lack of standardized approaches and protocols for scanning, analyzing, and reporting data often makes it difficult to understand exactly how analyses were performed, how to interpret results, and if findings can be broadly compared with other models and studies. This problem is compounded in analysis of the dentoalveolar complex by the presence of four distinct mineralized tissues: enamel, dentin, cementum, and alveolar bone.

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Biomineralization is regulated by inorganic pyrophosphate (PP), a potent physiological inhibitor of hydroxyapatite crystal growth. Progressive ankylosis protein (ANK) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) act to increase local extracellular levels of PP, inhibiting mineralization. The periodontal complex includes 2 mineralized tissues, cementum and alveolar bone (AB), both essential for tooth attachment.

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Osteoclasts (OCs) are bone-resorbing cells formed by the serial fusion of monocytes. In mice and humans, three distinct subsets of monocytes exist; however, it is unclear if all of them exhibit osteoclastogenic potential. Here we show that in wild-type (WT) mice, Ly6C and Ly6C monocytes are the primary source of OC formation when compared to Ly6C monocytes.

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Pyrophosphate (PP) serves as a potent and physiologically important regulator of mineralization, with systemic and local concentrations determined by several key regulators, including: tissue-nonspecific alkaline phosphatase (ALPL gene; TNAP protein), the progressive ankylosis protein (ANKH; ANK), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1; ENPP1). Results to date have indicated important roles for PP in cementum formation, and we addressed several gaps in knowledge by employing genetically edited mouse models where PP metabolism was disrupted and pharmacologically modulating PP in a PP-deficient mouse model. We demonstrate that acellular cementum growth is inversely proportional to PP levels, with reduced cementum in Alpl KO (increased PP levels) mice and excess cementum in Ank KO mice (decreased PP levels).

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It is well established that alterations in phosphate metabolism have a profound effect on hard and soft tissues of the oral cavity. The present-day clinical form of osteonecrosis of the jaw (ONJ) was preceded by phosphorus necrosis of the jaw, ca. 1860.

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Background: Inactivating mutations in the gene for cartilage-associated protein (CRTAP) cause osteogenesis imperfecta type VII in humans, with a phenotype that can include craniofacial defects. Dental and craniofacial manifestations have not been a focus of case reports to date. We analyzed the craniofacial and dental phenotype of Crtap mice by skull measurements, micro-computed tomography (micro-CT), histology, and immunohistochemistry.

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Unprecedented advances in genomics, data science, and biotechnology have ushered in a new era of health care in which interventions are increasingly tailored to individual patients. Precision-based approaches extend to oral health, which is essential to overall health. Harnessing the full potential of precision oral health will depend on research to more fully understand the factors that underlie health and contribute to disease-including the human genome, microbiome, epigenome, proteome, and others.

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This is the first study to our knowledge to report a novel mutation in the interferon regulatory factor 8 gene (IRF8 ) associated with multiple idiopathic tooth root resorption, a form of periodontal disease. The IRF8 variant in the highly conserved C-terminal motif is predicted to alter the protein structure, likely impairing IRF8 function. Functional assays demonstrated that the IRF8 mutant promoted osteoclastogenesis and failed to inhibit NFATc1-dependent transcriptional activation when compared with IRF8 control.

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The promise of tissue engineering and regenerative medicine to reduce the burden of disease and improve quality of life are widely acknowledged. Traditional tissue engineering and regenerative medicine approaches rely on generation of tissue constructs in vitro for subsequent transplantation or injection of exogenously manipulated cells into a host. While promising, few such therapies have succeeded in clinical practice.

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Previous studies revealed that cementum formation is tightly regulated by inorganic pyrophosphate (PP), a mineralization inhibitor. Local PP concentrations are determined by regulators, including ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which increases PP concentrations by adenosine triphosphate hydrolysis. Orthodontic forces stimulate alveolar bone remodelling, leading to orthodontic tooth movement (OTM).

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The periodontal complex is essential for tooth attachment and function and includes the mineralized tissues, cementum and alveolar bone, separated by the unmineralized periodontal ligament (PDL). To gain insights into factors regulating cementum-PDL and bone-PDL borders and protecting against ectopic calcification within the PDL, we employed a proteomic approach to analyze PDL tissue from progressive ankylosis knock-out (Ank) mice, featuring reduced PP, rapid cementogenesis, and excessive acellular cementum. Using this approach, we identified the matrix protein osteopontin (Spp1/OPN) as an elevated factor of interest in Ank mouse molar PDL.

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Chédiak-Higashi syndrome (CHS), a rare autosomal recessive disorder caused by mutations in the lysosomal trafficking regulator gene (LYST), is associated with aggressive periodontitis. It is suggested that LYST mutations affect the toll-like receptor (TLR)-mediated immunoinflammatory response, leading to frequent infections. This study sought to determine the periodontal status of patients with classic (severe) and atypical (milder) forms of CHS and the immunoregulatory functions of gingival fibroblasts in CHS patients.

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Mineralization of bones and teeth is tightly regulated by levels of extracellular inorganic phosphate (P) and pyrophosphate (PP). Three regulators that control pericellular concentrations of P and PP include tissue-nonspecific alkaline phosphatase (TNAP), progressive ankylosis protein (ANK), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Inactivation of these factors results in mineralization disorders affecting teeth and their supporting structures.

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