The guanine nucleotide exchange factor DOCK5 negatively regulates osteoblast differentiation and BMP2-induced bone regeneration via the MKK3/6 and p38 signaling pathways.

DOCK5 (dedicator of cytokinesis 5), a guanine nucleotide exchange factor for Rac1, has been implicated in BMP2-mediated osteoblast differentiation, but its specific role in osteogenesis and bone regeneration remained unclear. This study investigated the effect of DOCK5 on bone regeneration using C21, a DOCK5 chemical inhibitor, and Dock5-deficient mice. Osteoblast differentiation and bone regeneration were analyzed using bone marrow mesenchymal stem cells (BMSCs) and various animal models.

The transcription factor BBX regulates phosphate homeostasis through the modulation of FGF23.

Fibroblast growth factor 23 (FGF23) plays an important role in phosphate homeostasis, and increased FGF23 levels result in hypophosphatemia; however, the molecular mechanism underlying increased FGF23 expression has not been fully elucidated. In this study, we found that mice lacking the bobby sox homolog (Bbx) presented increased FGF23 expression and low phosphate levels in the serum and skeletal abnormalities such as a low bone mineral density (BMD) and bone volume (BV), as well as short and weak bones associated with low bone formation. Osteocyte-specific deletion of Bbx using Dmp-1-Cre resulted in similar skeletal abnormalities, elevated serum FGF23 levels, and reduced serum phosphate levels.

Author Correction: SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function.

[Image: see text]

Ibuprofen-induced multiorgan malformation during embryogenesis in Xenopus laevis (FETAX).

Ibuprofen, one of the most commonly prescribed nonsteroidal anti-inflammatory drugs, has not been fully assessed for embryonic toxicity in vertebrates. Here, we systematically assessed the embryotoxicity of ibuprofen in Xenopus laevis at various concentrations during embryogenesis. Embryos were treated with different concentrations of ibuprofen, ranging from 8 to 64 mg/L, at 23 °C for 96 h, and examined daily and evaluated at 72 hpf.

Increase of glutamate in satellite glial cells of the trigeminal ganglion in a rat model of craniofacial neuropathic pain.

Introduction: Satellite glial cells (SGCs) that envelop the cell bodies of neurons in sensory ganglia have been shown to both release glutamate, and be activated by glutamate in the context of nociceptive signaling. However, little is known about the subpopulations of SGCs that are activated following nerve injury and whether glutamate mechanisms in the SGCs are involved in the pathologic pain.

Methods: To address this issue, we used light and electron microscopic immunohistochemistry to examine the change in the glutamate levels in the SGCs and the structural relationship between neighboring neurons in the trigeminal ganglion (TG) in a rat model of craniofacial neuropathic pain, CCI-ION.

TonEBP Haploinsufficiency Attenuates Microglial Activation and Memory Deficits in Middle-Aged and Amyloid β Oligomer-Treated Mice.

Age-related microglial activation is associated with cognitive impairment. Tonicity-responsive enhancer-binding protein (TonEBP) is a critical mediator of microglial activation in response to neuroinflammation. However, the precise role of TonEBP in the middle-aged brain is not yet known.

Long-term tactile hypersensitivity after nerve crush injury in mice is characterized by the persistence of intact sensory axons.

Traumatic peripheral nerve injuries are at high risk of neuropathic pain for which novel effective therapies are urgently needed. Preclinical models of neuropathic pain typically involve irreversible ligation and/or nerve transection (neurotmesis). However, translation of findings to the clinic has so far been unsuccessful, raising questions on injury model validity and clinically relevance.

Synaptic connectivity of the TRPV1-positive trigeminal afferents in the rat lateral parabrachial nucleus.

Recent studies have shown a direct projection of nociceptive trigeminal afferents into the lateral parabrachial nucleus (LPBN). Information about the synaptic connectivity of these afferents may help understand how orofacial nociception is processed in the LPBN, which is known to be involved primarily in the affective aspect of pain. To address this issue, we investigated the synapses of the transient receptor potential vanilloid 1-positive (TRPV1+) trigeminal afferent terminals in the LPBN by immunostaining and serial section electron microscopy.

Suppressive effects of (-)-tubaic acid on RANKL-induced osteoclast differentiation and bone resorption.

Regulation of osteoclastogenesis and bone-resorbing activity can be an efficacious strategy for treating bone loss diseases because excessive osteoclastic bone resorption leads to the development of such diseases. Here, we investigated the role of (-)-tubaic acid, a thermal degradation product of rotenone, in osteoclast formation and function in an attempt to identify alternative natural compounds. (-)-Tubaic acid significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation at both the early and late stages, suggesting that (-)-tubaic acid affects the commitment and differentiation of osteoclast progenitors as well as the cell-cell fusion of mononuclear osteoclasts.

A Deficiency of the Psychiatric Risk Gene DLG2/PSD-93 Causes Excitatory Synaptic Deficits in the Dorsolateral Striatum.

Genetic variations resulting in the loss of function of the discs large homologs (DLG2)/postsynaptic density protein-93 (PSD-93) gene have been implicated in the increased risk for schizophrenia, intellectual disability, and autism spectrum disorders (ASDs). Previously, we have reported that mice lacking exon 14 of the gene ( mice) display autistic-like behaviors, including social deficits and increased repetitive behaviors, as well as suppressed spontaneous excitatory postsynaptic currents in the striatum. However, the neural substrate underpinning such aberrant synaptic network activity remains unclear.

Expression of Piezo2 in the Dental Pulp, Sensory Root, and Trigeminal Ganglion and Its Coexpression with Vesicular Glutamate Transporters.

Introduction: Information on the type of vesicular glutamate transporter (VGLUT) that is expressed in the Piezo2-positive (Piezo2+) neurons in the trigeminal ganglion (TG) and on the type of Piezo2+ axons and their distribution in the dental pulp is important for understanding dental pain elicited by mechanical stimuli and developing new therapeutic strategies.

Methods: We examined the expression of Piezo2 and its coexpression with VGLUT1 and VGLUT2 in rat TG, the sensory root, and human dental pulp using light and electron microscopic immunohistochemistry and quantitative analysis.

Results: VGLUT1 and VGLUT2 were expressed in the TG neurons.

Expression of Piezo1 in the Trigeminal Neurons and in the Axons That Innervate the Dental Pulp.

Information on the neurons and axons that express the mechanosensitive channel Piezo1 and its expression in axons innervating the dental pulp may help understand the nature of the Piezo1-mediated mechanosensation and the underlying mechanism of dentin sensitivity elicited by mechanical stimuli. For this, we here investigated the neurochemical properties of the neurons in the rat trigeminal ganglion (TG) and their axons in its sensory root that express Piezo1 and the expression of Piezo1 in the rat and human dental pulp by light and electron microscopic immunohistochemistry and quantitative analysis. Piezo1 was expressed mainly in medium-sized and large TG neurons.

The Cerebellar Cortex Receives Orofacial Proprioceptive Signals from the Supratrigeminal Nucleus via the Mossy Fiber Pathway in Rats.

Proprioceptive sensory information from muscle spindles is essential for the regulation of motor functions. However, little is known about the motor control regions in the cerebellar cortex that receive proprioceptive signals from muscle spindles distributed throughout the body, including the orofacial muscles. Therefore, in this study, we investigated the pattern of projections in the rat cerebellar cortex derived from the supratrigeminal nucleus (Su5), which conveys orofacial proprioceptive information from jaw-closing muscle spindles (JCMSs).

Ultrastructure of Rat Rostral Nucleus of the Solitary Tract Terminals in the Parabrachial Nucleus and Medullary Reticular Formation.

Neurons in the rostral nucleus of the solitary tract (rNST) receive taste information from the tongue and relay it mainly to the parabrachial nucleus (PBN) and the medullary reticular formation (RF) through two functionally different neural circuits. To help understand how the information from the rNST neurons is transmitted within these brainstem relay nuclei in the taste pathway, we examined the terminals of the rNST neurons in the PBN and RF by use of anterograde horseradish peroxidase (HRP) labeling, postembedding immunogold staining for glutamate, serial section electron microscopy, and quantitative analysis. Most of the anterogradely labeled, glutamate-immunopositive axon terminals made a synaptic contact with only a single postsynaptic element in PBN and RF, suggesting that the sensory information from rNST neurons, at the individual terminal level, is not passed to multiple target cells.

Efferent and afferent connections of supratrigeminal neurons conveying orofacial muscle proprioception in rats.

The supratrigeminal nucleus (Su5) is a key structure for controlling jaw movements; it receives proprioceptive sensation from jaw-closing muscle spindles (JCMSs) and sends projections to the trigeminal motor nucleus (Mo5). However, the central projections and regulation of JCMS proprioceptive sensation are not yet fully understood. Therefore, we aimed to reveal the efferent and afferent connections of the Su5 using neuronal tract tracings.

Protective Effect of Ciclopirox against Ovariectomy-Induced Bone Loss in Mice by Suppressing Osteoclast Formation and Function.

Postmenopausal osteoporosis is closely associated with excessive osteoclast formation and function, resulting in the loss of bone mass. Osteoclast-targeting agents have been developed to manage this disease. We examined the effects of ciclopirox on osteoclast differentiation and bone resorption in vitro and in vivo.

Ablation of dynamin-related protein 1 promotes diabetes-induced synaptic injury in the hippocampus.

Dynamin-related protein 1 (Drp1)-mediated mitochondrial dysfunction is associated with synaptic injury in the diabetic brain. However, the dysfunctional mitochondria by Drp1 deletion in the diabetic brain are poorly understood. Here, we investigated the effects of neuron-specific Drp1 deletion on synaptic damage and mitophagy in the hippocampus of a high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice.

PF-3845, a Fatty Acid Amide Hydrolase Inhibitor, Directly Suppresses Osteoclastogenesis through ERK and NF-κB Pathways In Vitro and Alveolar Bone Loss In Vivo.

Alveolar bone loss, the major feature of periodontitis, results from the activation of osteoclasts, which can consequently cause teeth to become loose and fall out; the development of drugs capable of suppressing excessive osteoclast differentiation and function is beneficial for periodontal disease patients. Given the difficulties associated with drug discovery, drug repurposing is an efficient approach for identifying alternative uses of commercially available compounds. Here, we examined the effects of PF-3845, a selective fatty acid amide hydrolase (FAAH) inhibitor, on receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclastogenesis, its function, and the therapeutic potential for the treatment of alveolar bone destruction in experimental periodontitis.

More Teeth and Posterior Balanced Occlusion Are a Key Determinant for Cognitive Function in the Elderly.

Age-related decline in cognitive function is a major challenge in geriatric healthcare. A possible explanation is that the tooth loss or low chewing ability is at cause of cognitive impairment or dementia. The study aimed to investigate the potential relationship between chewing ability and cognitive function in the elderly.

Widespread corticopetal projections from the oval paracentral nucleus of the intralaminar thalamic nuclei conveying orofacial proprioception in rats.

The oval paracentral nucleus (OPC) was initially isolated from the paracentral nucleus (PC) within the intralaminar thalamic nuclei in rats. We have recently shown that the rat OPC receives proprioceptive inputs from jaw-closing muscle spindles (JCMSs). However, it remains unknown which cortical areas receive thalamic inputs from the OPC, and whether the cortical areas receiving the OPC inputs are distinct from those receiving inputs from the other intralaminar nuclei and sensory thalamic nuclei.