Tissue-specific mineralization defects in the periodontium of the Hyp mouse model of X-linked hypophosphatemia

Coyac, Benjamin R.; Falgayrac, Guillaume; Baroukh, Brigitte; Slimani, Lotfi; Sadoine, Jérémy; Penel, Guillaume; Duplan, Martin Biosse; Schinke, Thorsten; Linglart, Agnès; McKee, Marc D.; Miller, Catherine; Bardet, Claire

doi:10.1016/j.bone.2017.07.026

Cited by 37 publications

(40 citation statements)

References 47 publications

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“…Individuals with XLH feature severe dental defects that cause tooth fractures and abscesses and increased prevalence of periodontal disorders that have not been well defined to date (Foster, Nociti, and Somerman 2014; Foster, Ramnitz, et al 2014; Biosse Duplan et al 2017; Chesher et al 2018; Skrinar et al 2019). We and others have reported histologic abnormalities in dentin and acellular cementum in Hyp mice (Abe et al 1989; Ogawa et al 2006; Fong, Chu, et al 2009) consistent with reported dental defects from XLH (Foster, Nociti, and Somerman 2014; Coyac et al 2017). However, many aspects of dentoalveolar pathology in XLH remain unclear, particularly how each mineralized tissue is comparatively affected and how the periodontium is impaired functionally.…”

Section: Introductionsupporting

confidence: 88%

Dentoalveolar Defects in the Hyp Mouse Model of X-linked Hypophosphatemia

et al. 2020

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Mutations in PHEX cause X-linked hypophosphatemia (XLH), a form of hypophosphatemic rickets. Hyp ( Phex mutant) mice recapitulate the XLH phenotype. Dental disorders are prevalent in individuals with XLH; however, underlying dentoalveolar defects remain incompletely understood. We analyzed Hyp mouse dentoalveolar defects at 42 and 90 d postnatal to comparatively define effects of XLH on dental formation and function. Phex mRNA was expressed by odontoblasts (dentin), osteocytes (bone), and cementocytes (cellular cementum) in wild-type (WT) mice. Enamel density was unaffected, though enamel volume was significantly reduced in Hyp mice. Dentin defects in Hyp molars were indicated histologically by wide predentin, thin dentin, and extensive interglobular dentin, confirming micro–computed tomography (micro-CT) findings of reduced dentin volume and density. Acellular cementum was thin and showed periodontal ligament detachment. Mechanical testing indicated dramatically altered periodontal mechanical properties in Hyp versus WT mice. Hyp mandibles demonstrated expanded alveolar bone with accumulation of osteoid, and micro-CT confirmed decreased bone volume fraction and alveolar bone density. Cellular cementum area was significantly increased in Hyp versus WT molars owing to accumulation of hypomineralized cementoid. Histology, scanning electron microscopy, and nanoindentation revealed hypomineralized “halos” surrounding Hyp cementocyte and osteocyte lacunae. Three-dimensional micro-CT analyses confirmed larger cementocyte/osteocyte lacunae and significantly reduced perilacunar mineral density. While long bone and alveolar bone osteocytes in Hyp mice overexpressed fibroblast growth factor 23 ( Fgf23), its expression in molars was much lower, with cementocyte Fgf23 expression particularly low. Expression and distribution of other selected markers were disturbed in Hyp versus WT long bone, alveolar bone, and cementum, including osteocyte/cementocyte marker dentin matrix protein 1 ( Dmp1). This study reports for the first time a quantitative analysis of the Hyp mouse dentoalveolar phenotype, including all mineralized tissues. Novel insights into cellular cementum provide evidence for a role for cementocytes in perilacunar mineralization and cementum biology.

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Section: Introductionsupporting

confidence: 88%

Dentoalveolar Defects in the Hyp Mouse Model of X-linked Hypophosphatemia

et al. 2020

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“…Conversely, increased OPN expression by cementum-associated cells in Enpp1 loss-of-function mice could influence osteoclast recruitment toward the root surface and away from bone, affecting resorptive activity at these locations. In a report on hypophosphatemic Hyp mutant mice, Coyac and colleagues found that increased OPN played a role in mineralization defects in dentin and alveolar bone, and sustained osteoclastic activity following ligature-induced periodontitis was associated with OPN-rich osteoid (Coyac et al 2017). However, OPN was not localized to the hypomineralized cellular cementum.…”

Section: Discussionmentioning

confidence: 99%

Reduced Orthodontic Tooth Movement in Enpp1 Mutant Mice with Hypercementosis

Wolf

Chavez

et al. 2018

J Dent Res

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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). To better understand how disturbed mineral metabolism and the resulting altered periodontal structures affect OTM, we employed Enpp1 mutant mice that feature reduced PP and increased cervical cementum in a model of OTM induced by a stretched closed-coil spring ligated between the maxillary left first molar and maxillary incisors. We analyzed tooth movement, osteoclast/odontoclast response, and tooth root resorption by micro-computed tomography, histology, histomorphometry, and immunohistochemistry. Preoperatively, we noted an altered periodontium in Enpp1 mutant mice, with significantly increased periodontal ligament (PDL) volume and thickness, as well as increased PDL-bone/tooth root surface area, compared to wild-type (WT) controls. After 11 d of orthodontic treatment, Enpp1 mutant mice displayed 38% reduced tooth movement versus WT mice. Molar roots in Enpp1 mutant mice exhibited less change in PDL width in compression and tension zones compared to WT mice. Root resorption was noted in both groups with no difference in average depths, but resorption lacunae in Enpp1 mutant mice were almost entirely limited to cementum, with 150% increased cementum resorption and 92% decreased dentin resorption. Osteoclast/odontoclast cells were reduced by 64% in Enpp1 mutant mice, with a predominance of tartrate-resistant acid phosphatase (TRAP)-positive cells on root surfaces, compared to WT mice. Increased numbers of TRAP-positive cells on root surfaces were associated with robust immunolocalization of osteopontin (OPN) and receptor-activator of NF-κB ligand (RANKL). Collectively, reduced response to orthodontic forces, decreased tooth movement, and altered osteoclast/odontoclast distribution suggests Enpp1 loss of function has direct effects on clastic function/recruitment and/or indirect effects on periodontal remodeling via altered periodontal structure or tissue mineralization.

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“…Individuals with XLH (a hypophosphatemic condition characterized by FGF23 overproduction [ 72 ]) exhibit various dental abnormalities. These abnormalities include the abnormal mineralization of dentin and increased pulp chambers (resulting in dental fractures), less abundant cementum (resulting in impaired tooth attachment), and an increased risk of periodontal disease and the development of dental abscesses [ 21 , 286 , 287 ]. Enamel is largely unaffected in XLH [ 288 ].…”

Section: Importance Of Dietary Phosphorus For Teeth (Or Dental Heamentioning

confidence: 99%

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

Serna

Bergwitz

2020

Nutrients

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Inorganic phosphate (Pi) plays a critical function in many tissues of the body: for example, as part of the hydroxyapatite in the skeleton and as a substrate for ATP synthesis. Pi is the main source of dietary phosphorus. Reduced bioavailability of Pi or excessive losses in the urine causes rickets and osteomalacia. While critical for health in normal amounts, dietary phosphorus is plentiful in the Western diet and is often added to foods as a preservative. This abundance of phosphorus may reduce longevity due to metabolic changes and tissue calcifications. In this review, we examine how dietary phosphorus is absorbed in the gut, current knowledge about Pi sensing, and endocrine regulation of Pi levels. Moreover, we also examine the roles of Pi in different tissues, the consequences of low and high dietary phosphorus in these tissues, and the implications for healthy aging.

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Tissue-specific mineralization defects in the periodontium of the Hyp mouse model of X-linked hypophosphatemia

Cited by 37 publications

References 47 publications

Dentoalveolar Defects in the Hyp Mouse Model of X-linked Hypophosphatemia

Dentoalveolar Defects in the Hyp Mouse Model of X-linked Hypophosphatemia

Reduced Orthodontic Tooth Movement in Enpp1 Mutant Mice with Hypercementosis

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

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