Abstract:Our study demonstrated for the first time that ACP cells could differentiate into an osteoblastic lineage via induction by Bmp2. The mechanism of ACP calcification likely involves osteoblastic differentiation modulated by Bmp2. Further studies targeting Bmp2 cascades could result in novel therapeutic interventions for recurrent ACP.
“…1 A-D) [ 1 , 2 ]. CP calcification mostly occurs in adamantinomatous craniopharyngioma (ACP), while calcification is rarely seen in squamous papillary craniopharyngioma (SPCP) [ 3 ]. Histologically, cell pattern of ACP is different from SPCP (Fig.…”
Section: Introductionmentioning
confidence: 99%
“…1 E, F ). This difference may be explained by the theory that ACP originates from odontogenic rests associated with remnants of Rathke’s pouch, while SPCP develops from buccal mucosa rests [ 3 , 4 ]. Fig.…”
Section: Introductionmentioning
confidence: 99%
“…In our previous study, we showed that ACP calcification can be considered a consequence of cell differentiation and might resemble the calcium deposition seen in osteogenesis and odontogenesis [ 3 ]. Expression of the core marker of osteogenic differentiation, Runt-related transcription factor 2 (Runx2), is high in severely calcified CPs.…”
Section: Introductionmentioning
confidence: 99%
“…Runx2 is a transcription factor that regulates downstream factors associated with calcium deposition during osteogenesis/odontogenesis [ 5 , 6 ]. In our previous work, we found that Bmp2-induced osteogenic differentiation and activation of Runx2 signaling play important roles in ACP calcification [ 3 ].…”
Background
Calcification of adamantinomatous craniopharyngioma (ACP) often causes problems with tumor resection, leading to a high incidence of deadly complications and tumor recurrence. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are 2 key enzymes that regulate histone acetylation and play important roles in tumor development. However, the roles of HAT and HDAC in the calcification and osteoblastic differentiation of ACP are not known.
Methods
In this study, primary cells were isolated from ACP tissues, and calcification was induced with bone morphogenetic protein 2 (Bmp2). HDAC3 expression was assessed in 12 tissue samples by Western blotting and immunohistochemistry. ACP calcification was assessed by Alizarin red staining. A luciferase reporter assay was performed to examine the interaction between miR-181b and the 3’-untranslated region of the polycomb chromobox 4 (CBX4) gene.
Results
Our results showed that the expression of HDAC3 was increased in the calcified ACP samples, but inhibition of HDAC3 promoted ACP cell calcification and osteoblastic differentiation. Mechanistically, HDAC3 nuclear translocation was suppressed by Bmp2, leading to Runx2 protein expression and Osterix, osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) mRNA expression. In addition, this process was suppressed by CBX4, which stabilized the nuclear localization of HDAC3. miR-181b, the expression of which was increased in Bmp2-induced ACP cells, directly targeted and decreased CBX4 expression and inhibited the nuclear localization of HDAC3.
Conclusions
Our results demonstrate that Bmp2 increases miR-181b levels to directly target and inhibit CBX4 expression, leading to a reduction in the CBX4-dependent regulation of HDAC3 nuclear translocation, which results in Runx2 activation/osteoblastic differentiation and calcium deposition in ACP. Further studies targeting these cascades may contribute to therapeutic interventions used for recurrent ACP.
“…1 A-D) [ 1 , 2 ]. CP calcification mostly occurs in adamantinomatous craniopharyngioma (ACP), while calcification is rarely seen in squamous papillary craniopharyngioma (SPCP) [ 3 ]. Histologically, cell pattern of ACP is different from SPCP (Fig.…”
Section: Introductionmentioning
confidence: 99%
“…1 E, F ). This difference may be explained by the theory that ACP originates from odontogenic rests associated with remnants of Rathke’s pouch, while SPCP develops from buccal mucosa rests [ 3 , 4 ]. Fig.…”
Section: Introductionmentioning
confidence: 99%
“…In our previous study, we showed that ACP calcification can be considered a consequence of cell differentiation and might resemble the calcium deposition seen in osteogenesis and odontogenesis [ 3 ]. Expression of the core marker of osteogenic differentiation, Runt-related transcription factor 2 (Runx2), is high in severely calcified CPs.…”
Section: Introductionmentioning
confidence: 99%
“…Runx2 is a transcription factor that regulates downstream factors associated with calcium deposition during osteogenesis/odontogenesis [ 5 , 6 ]. In our previous work, we found that Bmp2-induced osteogenic differentiation and activation of Runx2 signaling play important roles in ACP calcification [ 3 ].…”
Background
Calcification of adamantinomatous craniopharyngioma (ACP) often causes problems with tumor resection, leading to a high incidence of deadly complications and tumor recurrence. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are 2 key enzymes that regulate histone acetylation and play important roles in tumor development. However, the roles of HAT and HDAC in the calcification and osteoblastic differentiation of ACP are not known.
Methods
In this study, primary cells were isolated from ACP tissues, and calcification was induced with bone morphogenetic protein 2 (Bmp2). HDAC3 expression was assessed in 12 tissue samples by Western blotting and immunohistochemistry. ACP calcification was assessed by Alizarin red staining. A luciferase reporter assay was performed to examine the interaction between miR-181b and the 3’-untranslated region of the polycomb chromobox 4 (CBX4) gene.
Results
Our results showed that the expression of HDAC3 was increased in the calcified ACP samples, but inhibition of HDAC3 promoted ACP cell calcification and osteoblastic differentiation. Mechanistically, HDAC3 nuclear translocation was suppressed by Bmp2, leading to Runx2 protein expression and Osterix, osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) mRNA expression. In addition, this process was suppressed by CBX4, which stabilized the nuclear localization of HDAC3. miR-181b, the expression of which was increased in Bmp2-induced ACP cells, directly targeted and decreased CBX4 expression and inhibited the nuclear localization of HDAC3.
Conclusions
Our results demonstrate that Bmp2 increases miR-181b levels to directly target and inhibit CBX4 expression, leading to a reduction in the CBX4-dependent regulation of HDAC3 nuclear translocation, which results in Runx2 activation/osteoblastic differentiation and calcium deposition in ACP. Further studies targeting these cascades may contribute to therapeutic interventions used for recurrent ACP.
“…Among the factors, bone morphogenetic proteins (BMPs) have been proven to facilitate bone healing without bone tissue transfer (5). Studies have indicated that BMP-2, a protein of BMP family, has important roles in bone generation-associated processes, including osteoblastic differentiation (6), the healing process of segmental bone defects (7) and the capacity of bone marrow stromal cells (BMSCs) to undergo osteogenesis (8), and has been approved by the Food and Drug Administration of the USA for clinical use in the orthopedic and dental fields (9). However, large amounts of BMP-2 are required to achieve clinically significant bone regeneration and BMP-2 is easily inactivated by dilution or interaction with enzymes in the blood if applied alone by intravenous injection (10–12).…”
In the present study, the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered by chitosan (CS) microspheres on ectopic osteogenesis was investigated in a rat model. rhBMP-2-loaded CS microspheres and blank CS microspheres were prepared. A total of 24 male Sprague Dawley rats were divided into 4 groups with 6 rats in each group: The CS/rhBMP-2 group, the rhBMP-2 group, in which rhBMP-2 was directly implanted (rhBMP-2 dose in either group, 1 mg), the CS blank group and the control group. X-ray was performed at 4 weeks after ectopic osteogenesis surgery and micro-computed tomography (CT) examination was scheduled at 1, 2, 3 and 4 weeks after the surgery to determine ectopic osteogenesis in the different groups. Histological analysis, and determination of alkaline phosphatase (ALP) activity and calcium content were also performed. The mean diameter of the osteoid tissues was 1.1±0.3 cm (range, 0.8–1.4 cm) in the CS/rhBMP-2 group, which was significantly bigger than that in the rhBMP-2 group (0.3±0.1 cm; range, 0.1–0.4 cm) at 4 weeks after the surgery. X-ray analysis and micro-CT scan indicated that the area of high-density tissues and the radionuclide intensity, as well as bone volume in the 3-dimensional reconstruction were greatest in the CS/rhBMP-2 group, followed by those in the rhBMP-2 group. All parameters, including bone mineral density, tissue mineral density, tissue mineral content and bone volume fraction, were significantly higher in the CS/rhBMP-2 group at 3 and 4 weeks after the surgery, compared with those in the rhBMP-2 group. The histological analysis, ALP activity analysis and determination of calcium content revealed that the CS/rhBMP-2 system had the greatest ability to induce osteoblast differentiation. In conclusion, the CS/rhBMP-2 microsphere delivery system significantly enhanced the induction and promotion effects of rhBMP-2 regarding ectopic osteogenesis. The present study enhances the basic data available for future application of the CS/rhBMP-2 microspheres delivery system and provides a deeper understanding of the role of BMP-2 in bone regeneration.
The sellar region represents a complex anatomical area, composed of multiple structures of different embryological derivation, including the skull base and the pituitary gland, along with vascular, nervous, and meningeal structures. Masses arising in this region include benign and malignant lesions arising from the pituitary gland itself, but also from vestigial embryological residues or surrounding tissues, that may require different therapeutic approaches. While assessing sellar region masses, the combination of clinical presentation and imaging features is fundamental to define hypotheses about their nature. MR represents the imaging modality of choice, providing information about the site of the lesion, its imaging features, and relation with adjacent structures, while CT is useful to confirm the presence of lesion calcifications or to reveal tumor invasion of bony structures. The aim of this pictorial review is to provide an overview of the common neoplasms and tumor-like conditions of the sellar region, according to the 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition), with an emphasis on the radiologic-pathologic correlation. After a brief introduction on the anatomy of this region and the imaging and pathological techniques currently used, the most relevant MRI characteristics, clinical findings, and pathological data, including histologic and molecular features, will be shown and discussed, with the aim of facilitating an appropriate differential diagnosis among these entities.
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