Wnt pathway inhibitors are upregulated in XLH dental pulp cells in response to odontogenic differentiation

X-linked hypophosphatemia(XLH)represents the most common form of familial hypophosphatemia.Although significant advances have been made in the treatment of bone pathology,patients undergoing therapy continue to experience significantly decreased oral health-related quality of life.The following study addresses this persistent oral disease by further investigating the effect of DMP1 expression on the differentiation of XLH dental pulp cells.Dental pulp cells were isolated from the third molars of XLH and healthy controls and stable transduction of full-length human DMP1 were achieved.RNA sequencing was performed to evaluate the genetic changes following the induction of odontogenic differentiation.RNAseq data shows the upregulation of inhibitors of the canonical Wnt pathway in XLH cells,while constitutive expression of full-length DMP1 in XLH cells reversed this effect during odontogenic differentiation.These results imply that inhibition of the canonical Wnt pathway may contribute to the pathophysiology of XLH and suggest a new therapeutic strategy for the management of oral disease.

Sclerostin antibody improves alveolar bone quality in the Hyp mouse model of X-linked hypophosphatemia

X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads tohypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence ofdental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including thealveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (SclAb) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mousemodel of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male andfemale wild-type and Hyp littermates were injected with 25 mg·kg−1 of vehicle or Scl-Ab twice weekly beginning at 12 weeks of ageand euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineraldensity in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active(nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effecton the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend towardincreased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were notaffected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.

Inhibition of ciliary neurotrophic factor in a rat model of transected spinal cord

Ciliary neurotrophic factor （CNTF） dramatically increases following spinal cord injury and participates in the repair process, although some studies have shown that CNTF plays a role in promoting glial scar formation following spinal cord injury. The antibody closure model can be used to inhibit CNTF expression following spinal cord injury, thereby furthering the understanding of the role of CNTF in spinal cord injury repair. In the present experiment, spinal catheters were placed in the vertebral canal of spinal cord transected rats, and CNTF antibodies were injected following fixation of the paraspinal muscle catheter. At 24 hours after a single CNTF antibody injection, CNTF expression decreased in the thoracic and lumbar spinal cord and recovered to normal levels by 48 72 hours. CNTF antibody treatment can effectively block endogenous CNTF expression in the thoracic and lumbar spinal cord during an interval of less than 24 hours in transected rats.

Multiple metal sources in polymetallic W-Sn ore deposits revealed by mercury stable isotopes

Granite-related W-Sn ore systems are commonly associated with coeval Pb-Zn mineralization. It remains unclear whether these metals are derived from the same sources or not. Mercury(Hg) is a common minor component in such systems. Hg isotopes undergo unique mass-independent fractionation(expressed as Δ^(199)Hg values), which is mainly generated during Hg photochemical reactions on Earth's surface and not affected by magmatic-hydrothermal processes, offering an excellent opportunity to trace metal sources in hydrothermal systems. We observed near-zero Δ^(199)Hg values in wolframite(-0.10‰ to0.08‰, n=11), and in skarn-(-0.17‰ to 0.12‰, n=48) and greisen-type(-0.12‰ to 0.10‰, n=11) bulk tin-tungsten ore from eight major ore deposits in South China. These values are identical to those of coeval highly evolved granites(-0.13‰ to 0.12‰,n=49), supporting that Hg in W-Sn ores were sourced from granite. However, sulfides(e.g., pyrite, chalcopyrite, arsenopyrite,galena, and sphalerite) in these deposits exhibit negative to near-zero Δ^(199)Hg values(-0.42‰ to 0.09‰, n=124), which indicates a contribution of Hg and by inference other metals from both Precambrian basement rocks(Δ^(199)Hg<0) and ore-related granites.The study demonstrates that multiple sources of metals were involved in the formation of the polymetallic W-Sn deposits, and further highlights that extraction of metals from basement rocks may be a critical control on the formation of economically important mineralization of base metal sulfides(e.g., Pb, Zn) in granite-related magmatic-hydrothermal systems.