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ClC7 Cl− channels ( Clcn7) are crucial for osteoclastic bone resorption and have heterozygous mutation in autosomal osteopetrosis type II (ADO II) patients. Although extracellular acidification is known to induce ClC7 Cl− currents in Clcn7-transfected oocytes, other characteristics of this acid-induced Cl− current, as well as the effects of mutant Clcn7 in ADO II, remain to be determined. The present study showed that extracellular acidification evoked outward Cl− currents in mouse osteoclasts. Expression of wild-type human Clcn7 in HEK293 cells also induced a significant increase in acid-activated Cl− currents. These acid-activated Cl− currents were independent of intracellular acidification and [Ca2+] i increase. HEK293 cells with the Clcn7 mutation associated with ADO II at G215R did not display these Cl− currents. These results suggest that osteoclastic ClC7 Cl− channels are activated under extracellar acidification and suppressed in Clcn7 mutant associated with ADO II during bone resorption. [ABSTRACT FROM AUTHOR]

Bone destruction is a pathological hallmark of several chronic inflammatory diseases, including rheumatoid arthritis and periodontitis. Inflammation-induced bone loss of this sort results from elevated numbers of bone-resorbing osteoclasts. Gene targeting studies have shown that the transcription factor nuclear factor-?B (NF-?B) has a crucial role in osteoclast differentiation, and blocking NF-?B is a potential strategy for preventing inflammatory bone resorption. We tested this approach using a cell-permeable peptide inhibitor of the I?B-kinase complex, a crucial component of signal transduction pathways to NF-?B. The peptide inhibited RANKL-stimulated NF-?B activation and osteoclastogenesis both in vitro and in vivo. In addition, this peptide significantly reduced the severity of collagen-induced arthritis in mice by reducing levels of tumor necrosis factor-a and interleukin-1ß, abrogating joint swelling and reducing destruction of bone and cartilage. Therefore, selective inhibition of NF-?B activation offers an effective therapeutic approach for inhibiting chronic inflammatory diseases involving bone resorption. [ABSTRACT FROM AUTHOR]

Osteoclasts are multinucleated, bone-resorbing cells that show structural and functional differences between the resorbing and nonresorbing (motile) states during the bone resorption cycle. In the present study, we measured intracellular Ca[sup 2+] concentration ([Ca[sup 2+]][sub i]) in nonresorbing vs. resorbing rat osteoclasts. Basal [Ca[sup 2+]][sub i] in osteoclasts possessing pseudopodia (nonresorbing/ motile state) was around 110 nM and significantly higher than that in actin ring-forming osteoclasts (resorbing state, around 50 nM). In nonresorbing/motile osteoclasts, exposure to high K[sup +] reduced [Ca[sup 2+]][sub i], whereas high K[sup +] increased [Ca[sup 2+]][sub i] in resorbing state osteoclasts. In nonresorbing/motile ceils, membrane depolarization and hyperpolarization appiled by the patch-clamp technique decreased and increased [Ca[sup 2+]][sub i], respectively. Removal of extracellular Ca[sup 2+] or application of 300 µM La[sup 3+] reduced [Ca[sup 2+][sub i] to ∼50 nM in nonresorbing/motile osteoclasts, and high-K[sup +]-induced reduction of [Ca[sup 2+]][sub i] could not be observed under these conditions. Neither inhibition of intracellular Ca[sup 2+] stores or plasma membrane Ca[sup 2+] pumps nor blocking of L- and N-type Ca[sup 2+] channels significantly reduced [Ca[sup 2+][sub i]. Exposure to high K[sup +] inhibited the motility of nonresorbing osteoclasts and reduced the number of actin rings and pit formation in resorbing osteoclasts. These results indicate that in nonresorbing/ motile osteoclasts, a La[sup 3+]-sensitive Ca[sup 2+] entry pathway is continuously active under resting conditions, keeping [Ca[sup 2+]][sub i] high. Changes in membrane potential regulate osteoclastic motility by controlling the net amount of Ca[sup 2+] entry in a "reversed" voltage-dependent manner, i.e., depolarization decreases and hyperpolarization increases [Ca[sup 2+]][sub i]. [ABSTRACT FROM AUTHOR]

Examines the transport of salicylic acid across the placenta using the human trophoblast cell line BeWo. Measurement of the changes in intracellular pH during acid uptakes; Inhibition of L-lactic acid by salicylic acid and ibuprofen; Correlation of nonsteroidal anti-inflammatory drugs with lactate transporter inhibition.

Using the whole-cell patch-clamp technique in freshly isolated rat osteoclasts we examined the effects of estrogen on ionic channels. The predominant current was an inward rectifier K+ current (IKir). In the absence of non-osteoclastic cells, extracellularly applied 17β-estradiol (>0.1 µM) inhibited IKir, indicating that estrogen acts directly on osteoclasts. Application of 17β-estradiol (10 µM) for 10 min reduced IKir at the membrane potential of –120 mV to 70±15% of control. Removal of 17β-estradiol partially restored the inhibition. The inhibition of IKir was dependent on concentration and application time. Intracellularly applied 17β-estradiol had no effect on IKir. 17α-Estradiol also inhibited the IKir, whereas progesterone and testosterone had no effect. The inhibitory action of 17β-estradiol was not affected by guanosine 5′-O-(2-thiodiphosphate) (GDPβS), adenosine 3′,5′-cyclic monophosphothioate Rp diastereomer (Rp-cAMPS), okadaic acid, staurosporine and phorbol ester, and was independent of intracellular Ca2+ concentration ([Ca2+]i). With no influence from soluble factors secreted from non-osteoclastic cells, preincubation of the osteoclasts for more than 60 min with much lower concentrations of 17β-estradiol (1 and 10 nM) caused a reduction of IKir. In current-clamp configuration, application of 17β-estradiol (10 µM) depolarized the membrane associated with a decrease in a membrane conductance, indicating that 17β-estradiol inhibits IKir and depolarizes the membrane of osteoclasts. These results suggest that the 17β-estradiol-induced inhibition of IKir might be mediated via non-genomic mechanisms. This direct action of 17β-estradiol on osteoclasts may contribute to the regulation of [Ca2+]i and partially account for the protective effects of estrogen against bone loss. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) plays an important role in regulating the differentiation and function of osteoclasts. Calcium oscillations (Ca oscillations) are well-known phenomena in receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and bone resorption via calcineurin. Many modifiers are involved in the fine-tuning of Ca oscillations in osteoclasts. In addition to macrophage colony-stimulating factors (M-CSF; CSF-1) and RANKL, costimulatory signaling by immunoreceptor tyrosine-based activation motif-harboring adaptors is important for Ca oscillation generation and osteoclast differentiation. DNAX-activating protein of 12 kD is always necessary for osteoclastogenesis. In contrast, Fc receptor gamma (FcRγ) works as a key controller of osteoclastogenesis especially in inflammatory situation. FcRγ has a cofactor in fine-tuning of Ca oscillations. Some calcium channels and transporters are also necessary for Ca oscillations. Transient receptor potential (TRP) channels are well-known environmental sensors, and TRP vanilloid channels play an important role in osteoclastogenesis. Lysosomes, mitochondria, and endoplasmic reticulum (ER) are typical organelles for intracellular Ca2+ storage. Ryanodine receptor, inositol trisphosphate receptor, and sarco/endoplasmic reticulum Ca2+ ATPase on the ER modulate Ca oscillations. Research on Ca oscillations in osteoclasts has still many problems. Surprisingly, there is no objective definition of Ca oscillations. Causality between Ca oscillations and osteoclast differentiation and/or function remains to be examined. [ABSTRACT FROM AUTHOR]

Abstract: Epithelial to mesenchymal transition (EMT) plays an important role in tumor progression, and is an early step in carcinogenesis. Although reactive oxygen species (ROS) are known to be implicated in EMT in many tumor cell types, its exact role in EMT initiation in normal human cells, especially epidermal keratinocytes (NHEKs), remains unknown. To clarify whether ROS induce EMT in NHEKs, and to establish how ROS regulate EMT, we examined the effect of hydrogen peroxide (H2O2) on the expression of molecules involved in EMT and cell morphology in NHEKs. H2O2 altered the expression of EMT biomarkers, including downregulation of epithelial cadherin and upregulation of α-smooth muscle actin, through a transcriptional modulator, Snail1. H2O2 also induced epithelial to fibroblast-like morphological changes, together with upregulation of EMT biomarkers, and promoted phosphorylation of ERK1/2 and JNK in a time-dependent manner. Interestingly, H2O2 stimulated the expression and secretion of TGF-β1 in NHEKs. Exogenous TGF-β1 also induced the expression of EMT biomarkers. In contrast, neutralizing antibody anti-TGF-β1 antibody or inhibitor of TGF-β receptor type I suppressed the expression of EMT biomarkers. Our results suggest that ROS stimulated TGF-β1 secretion and MAPK activation, resulting in EMT initiation in NHEKs. [Copyright &y& Elsevier]

Amelogenesis consists of secretory, transition, maturation, and post-maturation stages, and the morphological changes of ameloblasts at each stage are closely related to their function. p130 Crk-associated substrate (Cas) is a scaffold protein that modulates essential cellular processes, including cell adhesion, cytoskeletal changes, and polarization. The expression of p130Cas was observed from the secretory stage to the maturation stage in ameloblasts. Epithelial cell-specific p130Cas-deficient (p130Cas Δepi- ) mice exhibited enamel hypomineralization with chalk-like white mandibular incisors in young mice and attrition in aged mouse molars. A micro-computed tomography analysis and Vickers micro-hardness testing showed thinner enamel, lower enamel mineral density and hardness in p130Cas Δepi- mice in comparison to p130Cas flox/flox mice. Scanning electron microscopy, and an energy dispersive X-ray spectroscopy analysis indicated the disturbance of the enamel rod structure and lower Ca and P contents in p130Cas Δepi- mice, respectively. The disorganized arrangement of ameloblasts, especially in the maturation stage, was observed in p130Cas Δepi- mice. Furthermore, expression levels of enamel matrix proteins, such as amelogenin and ameloblastin in the secretory stage, and functional markers, such as alkaline phosphatase and iron accumulation, and Na+/Ca2++K+-exchanger in the maturation stage were reduced in p130Cas Δepi- mice. These findings suggest that p130Cas plays important roles in amelogenesis (197 words). [Display omitted] • We examined the physiological role of p130Cas on amelogenesis using epithelial cell-specific p130Cas-deficient (p130Cas Δepi -) mice in vivo. • p130Cas Δepi- mice exhibited enamel hypomineralization with chalk-like white incisors in young mice and attrition in aged mouse molars. • Disorganized arrangement of ameloblasts were observed especially in the mature stage of p130Cas Δepi- mice. • Amelogenin and ameloblastin in the secretory stage, and alkaline phosphatase, iron accumulation, and Na+/Ca2++K+-exchanger in the maturation stage were reduced in ameloblasts from p130Cas Δepi- mice. • Our findings suggest that p130Cas plays important roles in amelogenesis. [ABSTRACT FROM AUTHOR]

Severe dental tissue damage induces odontoblast death, after which dental pulp stem and progenitor cells (DPSCs) differentiate into odontoblast-like cells, contributing to reparative dentin. However, the damage-induced mechanism that triggers this regeneration process is still not clear. We aimed to understand the effect of odontoblast death without hard tissue damage on dental regeneration. Herein, using a Cre/LoxP-based strategy, we demonstrated that cell-rich zone (CZ)-localizing Nestin-GFP-positive and Nestin-GFP-negative cells proliferate and differentiate into odontoblast-like cells in response to odontoblast depletion. The regenerated odontoblast-like cells played a role in reparative dentin formation. RNA-sequencing analysis revealed that the expression of odontoblast differentiation- and activation-related genes was upregulated in the pulp in response to odontoblast depletion even without damage to dental tissue. In this regenerative process, the expression of type I parathyroid hormone receptor (PTH1R) increased in the odontoblast-depleted pulp, thereby boosting dentin formation. The levels of PTH1R and its downstream mediator, i.e. , phosphorylated cyclic AMP response element-binding protein (Ser133) increased in the physically damaged pulp. Collectively, odontoblast death triggered the PTH1R cascade, which may represent a therapeutic target for inducing CZ-mediated dental regeneration. • Odontoblast death increases cell-rich zone-derived odontoblast-like cell counts. • Odontoblast death induces reparative dentin formation. • Odontoblast death results in pulpal PTH1R upregulation. • PTH1R contributes to dentin formation; it is upregulated in damaged dental pulp. [ABSTRACT FROM AUTHOR]

Background: Lectin-like oxidized low-density-lipoprotein receptor 1 (Lox-1) is the receptor for oxidized low-density lipoprotein (oxLDL), a mediator in dyslipidemia. Toll-like receptor (TLR)-2 and − 4 are receptors of lipopolysaccharide (LPS) from Porphyromonas gingivalis, a major pathogen of chronic periodontitis. Although some reports have demonstrated that periodontitis has an adverse effect on dyslipidemia, little is clear that the mechanism is explained the effects of dyslipidemia on osteoclastogenesis. We have hypothesized that osteoclast oxLDL has directly effect on osteoclasts (OCs), and therefore alveolar bone loss on periodontitis may be increased by dyslipidemia. The present study aimed to elucidate the effect of Lox-1 on osteoclastogenesis associated with TLRs in vitro. Methods: Mouse bone marrow cells (BMCs) were stimulated with macrophage colony-stimulating factor into bone marrow macrophages (BMMs). The cells were also stimulated with synthetic ligands for TLR2 (Pam3CSK4) or TLR4 (Lipid A), with or without receptor activator of nuclear factor kappa-B ligand (RANKL), and assessed for osteoclastogenesis by tartrate-resistant acid phosphatase (TRAP) staining, immunostaining, western blotting, flow activated cell sorting (FACS) analysis, real-time polymerase chain reaction (PCR), and reverse transcription PCR. Results: Lox-1 expression was significantly upregulated by Pam3CSK4 and Lipid A in BMCs (p < 0.05), but not in BMMs. FACS analysis identified that Pam3CSK4 upregulated RANK and Lox-1 expression in BMCs. TRAP-positive cells were not increased by stimulation with Pam3CSK4 alone, but were increased by stimulation with combination combined Pam3CSK and oxLDL. Expression of both Lox-1 and myeloid differentiation factor 88 (MyD88), an essential adaptor protein in the TLR signaling pathway, were suppressed by inhibitors of TLR2, TLR4 and mitogen-activated protein kinase (MAPK). Conclusions: This study supports that osteoclastogenesis is promoted under the coexistence of oxLDL by TLR2-induced upregulation of Lox-1 in BMCs. This indicates that periodontitis could worsen with progression of dyslipidemia. [ABSTRACT FROM AUTHOR]

Enamel forming ameloblasts move away from the dentino-enamel junction and also move relative to each other to establish enamel shape during the secretory stage of enamel development. Matrix metalloproteinase-20 (MMP20) is a tooth specific proteinase essential for proper enamel formation. We previously reported that MMP20 cleaves cadherins and may regulate ameloblast movement. Here, we used an Amelx promoter driven tdTomato reporter to label mouse ameloblasts. With these transgenic mice, we assessed ameloblast mobility group dynamics and gene expression. Three-dimensional imaging of mouse ameloblasts were observed in hemi-mandibles by using a tissue clearing technique. The three-dimensional ameloblast layer in Tg(Amelx-Mmp20) mice that overexpress MMP20 was uneven and the ameloblasts migrated away from this layer. Mouse ameloblast movement toward incisal tips was monitored by ex vivo time-lapse imaging. Gene expression related to cell migration and adhesion was analyzed in ameloblasts from wild-type mice, Mmp20 -/- mice with no functional MMP20 and from Tg(Amelx-Mmp20) overexpressing mice. Gene expression was altered in Mmp20 -/- and Tg(Amelx-Mmp20) mice compared to wild type. Among the genes assessed, those encoding laminins and a gap junction protein were upregulated in Mmp20 -/- mice. New techniques and findings described in this study may lead to an improved understanding of ameloblast movement during enamel formation., (© 2023. The Author(s).)

Transient receptor potential melastatin 7 (TRPM7) is a unique ion channel connected to a kinase domain. We previously demonstrated that Trpm7 expression is high in mouse ameloblasts and odontoblasts, and that amelogenesis is impaired in TRPM7 kinase-dead mice. Here, we analyzed TRPM7 function during amelogenesis in Keratin 14-Cre;Trpm7 fl/fl conditional knockout (cKO) mice and Trpm7 knockdown cell lines. cKO mice showed lesser tooth pigmentation than control mice and broken incisor tips. Enamel calcification and microhardness were lower in cKO mice. Electron probe microanalysis (EPMA) showed that the calcium and phosphorus contents in the enamel were lower in cKO mouse than in control mice. The ameloblast layer in cKO mice showed ameloblast dysplasia at the maturation stage. The morphological defects were observed in rat SF2 cells with Trpm7 knockdown. Compared with mock transfectants, the Trpm7 knockdown cell lines showed lower levels of calcification with Alizarin Red-positive staining and an impaired intercellular adhesion structures. These findings suggest that TRPM7 is a critical ion channel in enamel calcification for the effective morphogenesis of ameloblasts during amelogenesis., (© 2023 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

Transient receptor potential melastatin-subfamily member 7 (TRPM7) is a bifunctional protein containing a kinase fused to an ion channel permeated with cations, including Ca 2+ and Mg 2+ . Trpm7-null mice show embryonic lethality. Paired related homeobox 1 (Prx1) is expressed in undifferentiated mesenchymal cells such as the progenitor cells of both chondrocytes and osteoblasts involved in limb skeleton formation. Prx1-Cre-dependent Trpm7 mesenchymal-deleted mice were generated to examine the role of TRPM7 in bone development. We found that Prx1-Cre;Trpm7 fl/fl mice had shortened bones and impaired trabecular bone formation. Trabecular bone parameters, such as the bone volume (BV/TV), and trabecular number (Tb.N), were decreased in Prx1-Cre;Trpm7 fl/fl mice. The cortical bone parameters of cortical bone area (Ct.Ar) and cortical bone thickness (Ct.Th) were also down-regulated in these mice. The bone formation rate in Prx1-Cre;Trpm7 fl/fl mice was unchanged, but the hypertrophic area and cell size of the zone were smaller, and the expression of Col2a1, Col10a1 and Mmp13 was downregulated compared with control mice. These findings suggest impaired chondrogenesis in Prx1-Cre;Trpm7 fl/fl mice compared to control mice. The receptor activator of nuclear factor-kappa B ligand (RANKL) expression was increased, and RANKL-positive cells and osteoclasts were markedly accumulated in the boundary region between the growth plate and trabecular bone. In contrast, TRPM7 KR mice, which are kinase-dead mutants in which the TRPM7 ion channel function has not been altered, showed no marked differences in trabecular or cortical bone parameters compared to wild-type mice. These findings suggest that TRPM7 is critical as a cation channel rather than as a kinase in bone development via the regulation of chondrogenesis., Competing Interests: Declaration of competing interest All authors state that they have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Oral malignant melanoma, which frequently invades the hard palate or maxillary bone, is extremely rare and has a poor prognosis. Bone morphogenetic protein (BMP) is abundantly expressed in bone matrix and is highly expressed in malignant melanoma, inducing an aggressive phenotype. We examined the role of BMP signaling in the acquisition of an aggressive phenotype in melanoma cells in vitro and in vivo. In five cases, immunohistochemistry indicated the phosphorylation of Smad1/5 (p-Smad1/5) in the nuclei of melanoma cells. In the B16 mouse and A2058 human melanoma cell lines, BMP2, BMP4, or BMP7 induces morphological changes accompanied by the downregulation of E-cadherin, and the upregulation of N-cadherin and Snail, markers of epithelial-mesenchymal transition (EMT). BMP2 also stimulates cell invasion by increasing matrix metalloproteinase activity in B16 cells. These effects were canceled by the addition of LDN193189, a specific inhibitor of Smad1/5 signaling. In vivo, the injection of B16 cells expressing constitutively activated ALK3 enhanced zygoma destruction in comparison to empty B16 cells by increasing osteoclast numbers. These results suggest that the activation of BMP signaling induces EMT, thus driving the acquisition of an aggressive phenotype in malignant melanoma., (© 2021. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)

Purpose: Occlusal trauma, resulting in the destruction of alveolar bone, is a form of periodontal disease caused by excessive mechanical stress (MS) during hyperocclusion. Previously, we showed that CC chemokine ligand (CCL) 2/CCR2 receptor axis plays a crucial role in MS-dependent osteoclastogenesis. However, in the previous work, we were unable to precisely measure changes in alveolar bone profiles. In the present study, we sought to establish a precise method for evaluating alveolar bone resorption induced by hyperocclusion using micro-computed tomography., Methods: Under anesthesia, a stainless steel wire was attached to the molars of 5-week-old C57/BL6 wild-type (WT) mice, CCL2 -/- mice, and CCR2 -/- mice to induce occlusal force overload. At days 0 and 7, hard tissue samples were harvested and analyzed by micro-computed tomography., Results: In the WT mice, bone mineral density of the alveolar bone was significantly decreased at day 7 as compared with day 0, with marked alveolar bone resorption observed. Similarly, significant alveolar bone resorption was observed in the CCL2 -/- and CCR2 -/- mice at day 7 as compared with day 0., Conclusions: Micro-computed tomographic images can be used to measure changes in bone mineral density in a mouse model of hyperocclusion. This method may be useful for further investigating bone changes in other periodontal disease research fields., (Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.)

Hajdu-Cheney syndrome (HCS), a rare autosomal disorder caused by heterozygous mutations in NOTCH2, is clinically characterized by acro-osteolysis, severe osteoporosis, short stature, neurological symptoms, cardiovascular defects, and polycystic kidneys. Recent studies identified that aberrant NOTCH2 signaling and consequent osteoclast hyperactivity are closely associated with the bone-related disorder pathogenesis, but the exact molecular mechanisms remain unclear. Here, we demonstrate that sustained osteoclast activity is largely due to accumulation of NOTCH2 carrying a truncated C terminus that escapes FBW7-mediated ubiquitination and degradation. Mice with osteoclast-specific Fbw7 ablation revealed osteoporotic phenotypes reminiscent of HCS, due to elevated Notch2 signaling. Importantly, administration of Notch inhibitors in Fbw7 conditional knockout mice alleviated progressive bone resorption. These findings highlight the molecular basis of HCS pathogenesis and provide clinical insights into potential targeted therapeutic strategies for skeletal disorders associated with the aberrant FBW7/NOTCH2 pathway as observed in patients with HCS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The SCF β-TRCP E3 ubiquitin ligase complex plays pivotal roles in normal cellular physiology and in pathophysiological conditions. Identification of β-transducin repeat-containing protein (β-TRCP) substrates is therefore critical to understand SCF β-TRCP biology and function. We used a β-TRCP-phosphodegron motif-specific antibody in a β-TRCP substrate screen coupled with tandem mass spectrometry and identified multiple β-TRCP substrates. One of these substrates was Lipin1, an enzyme and suppressor of the family of sterol regulatory element-binding protein (SREBP) transcription factors, which activate genes encoding lipogenic factors. We showed that SCF β-TRCP specifically interacted with and promoted the polyubiquitination of Lipin1 in a manner that required phosphorylation of Lipin1 by mechanistic target of rapamycin 1 (mTORC1) and casein kinase I (CKI). β-TRCP depletion in HepG2 hepatocellular carcinoma cells resulted in increased Lipin1 protein abundance, suppression of SREBP-dependent gene expression, and attenuation of triglyceride synthesis. Moreover, β-TRCP1 knockout mice showed increased Lipin1 protein abundance and were protected from hepatic steatosis induced by a high-fat diet. Together, these data reveal a critical physiological function of β-TRCP in regulating hepatic lipid metabolic homeostasis in part through modulating Lipin1 stability., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2017, American Association for the Advancement of Science.)

Objectives: It is known that excessive mechanical force exerted by hyperocclusion induces occlusal trauma. However, the mechanism of the process remains unclear. In the present study, we employed an in vivo hyperocclusion rodent model to examine morphological and biological mechanisms of occlusal trauma in periodontal ligament tissue., Design: To investigate alveolar bone resorption, tooth sections were stained to detect osteoclasts. To investigate the relationship between hyperocclusion and the regeneration of the cell matrix, we examined the effect of hyperocclusal force on the expression of collagens using immunohistochemistry and quantitative PCR methods., Results: The arrangement of collagen fibers in the furcation area of the teeth was undisturbed before hyperocclusion (control). Type I collagen was localized in the extracellular area at the furcation and there was faint expression and localization of type XII collagen in the periodontal ligament. The number of osteoclasts significantly increased in the furcation and lingual cervical regions on day 4 after hyperocclusion was induced. Type XII collagens were gradually up-regulated following the induction of hyperocclusion, in a time-dependent manner. Although type I collagen mRNA expression was stable before and after hyperocclusion, type XII collagen mRNA was significantly up-regulated on day 2 and day 4 after hyperocclusion treatment., Conclusions: Our findings indicate that hyperocclusal force predominantly up-regulates the expression of type XII collagen in periodontal tissue, but not type I collagen, suggesting that there is a mechanism for regeneration of periodontal tissues as a response to occlusal trauma., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Although it is believed that odontoclasts, which mediated root resorption of deciduous teeth, possess common properties to osteoclasts, these regulatory mechanisms differ from osteoclastic bone resorption. It is well established that calcitonin receptor is an important osteoclast marker and that calcitonin is a potent inhibitory hormone of osteoclastic bone resorption. However, the presence and function of calcitonin receptors in human odontoclasts are still controversial. We summarize the physiological properties and differentiation mechanisms of odontoclasts, and the effects of calcitonin on root resorption, including our recent results using human odontoclasts and periodontal ligament cells freshly isolated from deciduous tooth roots.