Osteoclasts are specialized cells essential for bone resorption, a crucial process in bone remodeling, and dysregulation of osteoclastogenesis can lead to pathological bone loss such as osteoporosis and rheumatoid arthritis. Therefore, understanding the precise mechanisms governing osteoclast differentiation is crucial for developing effective therapies for skeletal diseases. In osteoclastogenesis, as well as other differentiated cells, it is well understood that cell cycle arrest is essential for terminal differentiation and is tightly regulated by CDK inhibitors such as Cip/Kip family and Ink4 family protein. In this manuscript, we identified p15Ink4b, a member of the Ink4 family, as a novel regulator of osteoclastogenesis by comprehensive single-cell RNA sequence data reanalyzing. Furthermore, histological analysis and in vitro osteoclast differentiation assay revealed that p15Ink4b functionally regulates osteoclastogenesis. Our findings may not only provide insights into the molecular mechanisms of osteoclast differentiation but also underscore the potential of harnessing cell cycle mechanisms to develop novel therapeutic strategies for bone diseases.
purpose. To investigate the effect of a peptide (PHSRN) corresponding to the second cell-binding site of fibronectin on the expression of ZO-1 in cultured human corneal epithelial (HCE) cells. methods. The effects of the PHSRN peptide on the expression of ZO-1, -2, and -3; claudin; and occludin were determined by reverse transcription-polymerase chain reaction (RT-PCR), immunoblot, and immunofluorescence analyses. Phosphorylation of mitogen-activated protein kinases (MAPKs) and the transcription factor c-Jun was assessed with a multiplex analysis system and immunoblot analysis. The barrier function of cultured HCE cells was evaluated by measurement of transepithelial electrical resistance. results. RT-PCR and immunoblot analyses revealed the PHSRN peptide increased the amounts of ZO-1 mRNA and protein in HCE cells in a concentration- and time-dependent manner. The PHSRN peptide had no effect on the expression of ZO-2, ZO-3, claudin, or occludin. Immunofluorescence microscopy showed that the PHSRN peptide did not affect the localization of ZO-1 at the interfaces of neighboring cells. The PHSRN peptide induced the phosphorylation of the MAPKs ERK, p38, and JNK as well as that of c-Jun. The upregulation of ZO-1 expression by the PHSRN peptide was blocked by inhibitors of signaling by ERK (PD098059), p38 (SB203580), or JNK (JNK inhibitor II). The PHSRN peptide had no effect on the transepithelial electrical resistance of cultured HCE cells. conclusions. The PHSRN peptide upregulated the expression of ZO-1 through activation of MAPK signaling pathways in HCE cells. This effect of the PHSRN sequence of fibronectin may contribute to the formation of tight junctions and play an important role in the differentiation of corneal epithelial cells.
To investigate the changes in corneal shape and optical performance during and after discontinuation of overnight orthokeratology for correction of myopia.Both eyes of 15 subjects were fitted with overnight reverse-geometry orthokeratology lenses, which were then worn for >4 hr overnight for 52 weeks. Subjects were free of ocular disease and had a corrected visual acuity of > or =1.0. Refractive correction, uncorrected visual acuity, corneal topography, and contrast sensitivity (at 4 spatial frequencies) were measured under photopic conditions.Refractive error (spherical equivalent) and contrast sensitivity were decreased, whereas uncorrected visual acuity, the surface asymmetry index, and the surface regularity index were increased, 1 week after the onset of overnight orthokeratology and remained so during the 52 weeks of treatment. These parameters had largely returned to baseline values by 8 weeks after treatment discontinuation.Overnight orthokeratology improved uncorrected visual acuity and reduced refractive error but increased corneal irregularity and impaired contrast sensitivity. However, these changes in visual function and corneal shape were reversed after discontinuation of orthokeratology lens wear.
Objectives: To determine whether Aphex KC, a newly designed rigid gas-permeable (RGP) contact lens with dual aspherical base curves, improves visual acuity and lens wear time in patients with keratoconus. Methods: We performed a retrospective analysis of a noncomparative case series of 29 eyes of 24 patients with keratoconus who were intolerant of spherical RGP contact lenses and were fitted with Aphex KC at Yamaguchi University Hospital. Visual acuity and lens wear time were recorded as primary outcome measures at follow-up visits. Six patients with a follow-up period of <1 year were excluded from data analysis. At the last follow-up visit, 86.2% of eyes (25 eyes of 20 patients) continued to wear Aphex KC. Results: Mean uncorrected visual acuity was 1.4 LogMAR (20/500 in Snellen notation) for the 29 eyes enrolled in the study. Mean best-corrected visual acuity was 0.1 LogMAR (20/25) with Aphex KC and 0.7 LogMAR (20/111) with glasses (P < 0.001). A total of 19 eyes (65.5%) had a best-corrected visual acuity of 0.2 LogMAR (20/29) or better with Aphex KC. The mean ± SD wear time was 12.6 ± 3.2 hr/day with Aphex KC and 0.4 ± 0.7 hr/day with a previously prescribed spherical RGP contact lens (P = 1 × 10−12). The numbers of eyes wearing Aphex KC or the previously prescribed RGP contact lens for >12 hr/day were 26 and 0, respectively (P = 1 × 10−12). No serious complications of Aphex KC wear were observed. Conclusions: Fitting of an Aphex KC lens improved visual acuity and increased lens wear time in keratoconus patients who were intolerant of a spherical RGP contact lens. Aphex KC thus provides a viable alternative for management of such patients.
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