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X-linked hypophosphatemia (XLH) is an inherited disorder caused by inactivating mutations in the PHEX gene leading to renal phosphate wasting, rickets and osteomalacia. XLH is also associated with dentoalveolar mineralization defects in tooth enamel, dentin and cementum, and in alveolar bone, which lead to an increased prevalence of dental abscesses, periodontal disease and tooth loss. Genetic mouse experiments, and deficiencies in XLH patient therapies where treatments do not fully ameliorate mineralization defects, suggest that other pathogenic mechanisms may exist in XLH. The mineralization-inhibiting, secreted extracellular matrix phosphoprotein osteopontin (OPN, gene Spp1) is a substrate for the PHEX enzyme whereby extensive and inactivating degradation of inhibitory OPN by PHEX facilitates mineralization. Conversely, excess OPN accumulation in skeletal and dental tissues - for example in XLH where inactivating mutations in the PHEX gene limit degradation of inhibitory OPN, or as occurs in Fgf23-null mice - contributes to mineralization defects. We hypothesized that Spp1/OPN ablation in Hyp mice (a mouse model for XLH) would reduce dentoalveolar mineralization defects. Immunostaining revealed increased OPN in Hyp vs. wild-type (WT) alveolar bone, particularly in osteocyte lacunocanalicular networks where Hyp mice have characteristic hypomineralized peri-osteocytic lesions (POLs). Micro-computed tomography and histology showed that ablation of Spp1 in Hyp mice (Hyp;Spp1 -/- ) on a normal diet did not ameliorate bulk defects in enamel, dentin, or alveolar bone. On a high-phosphate diet, both Hyp and Hyp;Spp1 -/- mice showed improved mineralization of enamel, dentin, and alveolar bone. Silver staining indicated Spp1 ablation did not improve alveolar or mandibular bone osteocyte POLs in Hyp mice; however, they were normalized by a high-phosphate diet in both Hyp and Hyp;Spp1 -/- mice, although inducing increased OPN. Collectively, these data indicate that despite changes in OPN content in the dentoalveolar mineralized tissues, there exist other compensatory mineralization mechanisms that arise from knockout of Spp1/OPN in the Hyp background., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cementum is a mineralized tissue that covers tooth roots and functions in the periodontal attachment complex. Cementocytes, resident cells of cellular cementum, share many characteristics with osteocytes, are mechanoresponsive cells that direct bone remodeling based on changes in loading. We hypothesized that cementocytes play a key role during orthodontic tooth movement (OTM). To test this hypothesis, we used 8-week-old male Wistar rats in a model of OTM for 2, 7, or 14 days (0.5 N), whereas unloaded contralateral teeth served as controls. Tissue and cell responses were analyzed by high-resolution micro-computed tomography, histology, tartrate-resistant acid phosphatase staining for odontoclasts/osteoclasts, and transmission electron microscopy. In addition, laser capture microdissection was used to collect cellular cementum, and extracted proteins were identified by liquid chromatography coupled to tandem mass spectrometry. The OTM model successfully moved first molars mesially more than 250 μm by 14 days introducing apoptosis in a small number of cementocytes and areas of root resorption on mesial and distal aspects. Cementocytes showed increased nuclear size and proportion of euchromatin suggesting cellular activity. Proteomic analysis identified 168 proteins in cellular cementum with 21 proteins found only in OTM sites and 54 proteins only present in control samples. OTM-down-regulated several extracellular matrix proteins, including decorin, biglycan, asporin, and periostin, localized to cementum and PDL by immunostaining. Furthermore, type IV collagen (COL14A1) was the protein most down-regulated (-45-fold) by OTM and immunolocalized to cells at the cementum-dentin junction. Eleven keratins were significantly increased by OTM, and a pan-keratin antibody indicated keratin localization primarily in epithelial remnants of Hertwig's epithelial root sheath. These experiments provide new insights into biological responses of cementocytes and cellular cementum to OTM., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The aim of the present study was to evaluate the toxicity of magnetic iron oxide nanoparticles (MIONs) which were synthesized using carob leaf extract on various brain areas of Wistar rats., Main Methods: Carob leaf synthesized-MIONs were characterized using different techniques: Dynamic Light Scattering (DLS), Transmission Electron Microscope (TEM), UV-vis spectrophotometer, Fourier Transform infrared (FTIR), X-Ray Diffraction (XRD) and Atomic Force Microscope (AFM). The toxicity of MIONs in vivo was evaluated by: monitoring rat's body weight, measuring iron content in different brain areas, evaluating some oxidative stress parameters, estimating acetylcholinesterase (AChE) in addition to histopathological investigations., Key Findings: The present study demonstrated no body weight changes of MIONs- treated rats. According to the conditions of the present study, the hippocampus and striatum were the most affected areas and demonstrated neuronal degeneration due to MIONs exposure. MIONs treatment of Wistar rats, also affected the iron homeostasis in both striatum and midbrain by decreasing iron content in these areas. The least affected areas were thalamus and cerebellum. The histopathological examination of brain areas demonstrated moderate neuronal degeneration in hippocampus and striatum, mild neuronal degeneration in cortex and slight degeneration in hypothalamus and pons-medulla areas were detected., Significance: The results suggested that MIONs have a toxic impact on different brain areas and the effect varies according to the brain area., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2019 Elsevier B.V. All rights reserved.)