Rapid skull growth marker and application thereof

Abstract

The invention belongs to the technical field of medicine, discloses a skull rapid growth marker and application thereof, and provides a skull rapid growth marker based on a pressure / dura mater FAK-Twist1 pathway and an application method of the marker in child skull defect repair. By detecting the expression level of the marker, the growth and development state of the pediatric skull can be accurately judged, and a scientific basis is provided for clinical doctors to select proper skull repair opportunities, so that the success rate and safety of pediatric skull defect repair operations are improved, and postoperative complications are reduced. The rapid skull growth markers determined by the invention are closely related to the growth and development mechanism of the child skull based on a pressure / dura mater FAK-Twist1 pathway, and the growth state of the skull can be accurately reflected by detecting the expression level of the markers, so that a reliable diagnostic basis is provided for opportunity selection of a child skull defect repair operation.

Description

Technical Field

[0001] This invention belongs to the field of medical technology, and in particular relates to a marker for rapid skull growth and its application. Background Technology

[0002] Skull defects in children are common in neurosurgery, with diverse causes including congenital skull malformations, traumatic brain injury, and craniocerebral surgery. However, the surgical repair of skull defects in children remains highly controversial. Because the pediatric skull is in a continuous developmental stage, inappropriate skull repair may restrict normal skull growth and development, leading to serious consequences such as skull deformities. Therefore, identifying the key regulatory factors affecting the growth and development of the pediatric skull is crucial for determining the optimal timing and method of skull repair.

[0003] Currently, relevant literature reports that the immature dura mater plays an important role in the osteogenic and remodeling processes of the developing skull (such as cranial suture closure), but the specific molecular mechanisms are not yet fully elucidated. During skull development, intracranial pressure gradually increases, and pressure, as an important physical factor, has been proven to influence skull growth and remodeling. Fibroblast growth factor receptor substrate 2α (FAK), as a key molecule in cellular stress sensing and transmission, plays a central role in the cellular response to pressure signals. Twist1 is an important transcriptional regulatory protein in dura mater cells that regulates the expression of soluble bone growth factor. Further research has revealed the existence of the FAK-Twist1 signaling pathway within cells, which may play a crucial regulatory role in skull development.

[0004] Based on the results of high-throughput sequencing of the dura mater in model animals, the research group proposed the theoretical hypothesis that "the pressure / dura mater FAK-Twist1 pathway regulates skull growth during development." However, there is currently a lack of key biomarkers based on this theory to guide the repair and treatment of pediatric skull defects. Therefore, it is urgent to discover a biomarker that can reflect the rapid growth state of the pediatric skull in order to achieve early and safe repair of pediatric skull defects.

[0005] Based on the above analysis, the problems and shortcomings of the existing technology are as follows:

[0006] Currently, there is a lack of key biomarkers based on this theory to guide the repair and treatment of pediatric skull defects. Therefore, there is an urgent need to discover a biomarker that can reflect the rapid growth of the pediatric skull in order to achieve early and safe repair of pediatric skull defects. Summary of the Invention

[0007] To address the problems existing in the prior art, this invention provides a marker for rapid skull growth and its application.

[0008] The present invention is achieved by providing a marker for rapid skull growth, comprising: FAK, Twist1, and a soluble bone growth factor regulated by Twist1, wherein the soluble bone growth factor is selected from at least one of bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β1 (TGF-β1).

[0009] Another object of the present invention is to provide a method for applying a marker of rapid skull growth:

[0010] Step 1: Collect dura mater tissue and / or blood samples from pediatric patients with skull defects;

[0011] Step 2: Detect the mRNA and / or protein expression levels of FAK, Twist1, BMP-2, and TGF-β1 in the sample;

[0012] Step 3: Assess the patient's skull growth and development status based on the marker expression levels to determine the timing of cranioplasty.

[0013] Step 4: Perform cranial defect repair surgery at the appropriate time;

[0014] Step 5: Postoperatively, the expression levels of biomarkers are monitored regularly to assess surgical outcomes and patient prognosis.

[0015] Furthermore, the test sample:

[0016] Histological and molecular biological techniques were used to test the samples;

[0017] Histological techniques: Immunohistochemical staining was used to observe the localization and expression of FAK and Twist1 in the dura mater tissue;

[0018] Molecular biology techniques: real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the mRNA and protein expression levels of FAK, Twist1, and related bone growth factors (BMP-2 and TGF-β1) in dura mater tissue and blood samples, respectively.

[0019] Animal model testing and in vitro cell culture testing.

[0020] Furthermore, the animal model testing involves establishing an animal model of pediatric skull development and defect repair. Dura mater tissue and blood samples are collected from the animals at different developmental stages and repair time points. The biomarkers are detected using the same detection technology as clinical samples to verify the expression patterns of the biomarkers in the animal model and their correlation with skull growth and development.

[0021] Furthermore, the in vitro cell culture assay: Dura mater cells were cultured in vitro, and intracranial pressure changes were simulated by applying different pressure stimuli. The above-mentioned molecular biology techniques were used to detect the expression changes of FAK, Twist1 and related bone growth factors in the cells before and after pressure stimulation, so as to further clarify the regulatory role of the pressure / dura mater FAK-Twist1 pathway on the expression of biomarkers.

[0022] Furthermore, the postoperative periodic monitoring includes: After cranioplasty, blood samples are collected periodically to detect biomarker expression levels, monitoring skull growth and development and surgical outcomes. A gradual increase in biomarker expression levels indicates good skull growth and recovery; conversely, persistently abnormal or declining levels may indicate poor surgical outcomes or complications, requiring timely treatment.

[0023] Based on the above technical solutions and the technical problems solved, the advantages and positive effects of the technical solution to be protected by this invention are as follows:

[0024] First, this invention provides a marker for rapid skull growth based on the pressure / dura mater FAK-Twist1 pathway, and a method for applying this marker in the repair of pediatric skull defects. By detecting the expression level of this marker, the growth and development status of the pediatric skull can be accurately determined, providing a scientific basis for clinicians to select the appropriate timing for skull repair, thereby improving the success rate and safety of pediatric skull defect repair surgery and reducing the occurrence of postoperative complications.

[0025] 1. High diagnostic accuracy: The rapid skull growth markers identified in this invention are based on the pressure / dura mater FAK-Twist1 pathway, which is closely related to the growth and development mechanism of the pediatric skull. By detecting the expression level of these markers, the growth status of the skull can be accurately reflected, providing a reliable diagnostic basis for the selection of the timing of pediatric skull defect repair surgery.

[0026] 2. Personalized treatment: Through biomarker testing, a personalized cranioplasty plan can be developed based on each patient's specific situation, avoiding a one-size-fits-all approach, improving the success rate and safety of the surgery, and reducing the occurrence of complications such as skull deformities caused by inappropriate surgical timing.

[0027] 3. Prognostic assessment: Continuous monitoring of biomarkers after surgery helps to assess the effectiveness of cranioplasty and the patient's prognosis, identify potential problems in a timely manner and take intervention measures to improve the patient's treatment effect and quality of life.

[0028] 4. Sufficient scientific basis: This invention combines multiple research methods such as clinical samples, model animals, and in vitro cell culture to verify the correlation between biomarkers and pediatric skull growth and development from multiple levels, providing a solid scientific basis for the application of biomarkers.

[0029] Secondly, does the technical solution of this invention solve a technical problem that people have long desired to solve but have never been able to successfully address?

[0030] This invention relates to the field of pediatric skull growth assessment technology, and specifically provides a method for assessing the rapid growth phase of the skull in children based on specific gene markers. This method creatively combines FAK, Twist1, and bone growth-related factors (BMP-2, TGF-β1) from dura mater tissue and blood samples into a set of joint diagnostic gene biomarkers. The expression levels (significantly elevated) of these regulatory genes in the dura mater or blood of children with skull defects are used as early warning indicators. Compared to traditional MRI and CT scans, or reliance on clinicians' subjective assessment of surgical timing based on treatment guidelines, the gene-based joint detection method provided by this invention offers higher objectivity and accuracy. This method can be widely applied to children with skull defects during the rapid growth and development phase of the skull, accurately detecting their skull growth and development status to determine whether the peak of rapid growth has passed, thus providing a scientific basis for selecting the timing of skull repair surgery. Based on the above genetic testing results, the growth rate of the child's skull can be further assessed, thereby determining the repair method (such as material selection and surgical plan design) and the optimal repair time for skull defects. This method is simple to operate, effectively reducing reliance on specific large imaging equipment and the personal experience of senior physicians. It provides a new reference tool for judging the timing of pediatric skull defect repair and formulating repair methods, which helps to promote the precision treatment of pediatric skull defects. Attached Figure Description

[0031] Figure 1 This is a flowchart of the method for applying rapid skull growth markers provided in an embodiment of the present invention.

[0032] Figure 2 This is a flowchart of the model animal detection method provided in the embodiments of the present invention.

[0033] Figure 3 This is a structural block diagram of the skull rapid growth marker application system provided in an embodiment of the present invention.

[0034] Figure 4 These are images of dura mater tissue and blood samples collected from rats in the model group and control group on postoperative days 3, 7, 14 and 21, as provided in this embodiment of the invention.

[0035] Figure 5This refers to the change in the expression of biomarkers after inhibiting FAK activity, as provided in the embodiments of the present invention. Detailed Implementation

[0036] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0037] In the field of skull defect repair and craniofacial surgery, current technologies have significant limitations in determining the optimal timing for repair. Traditional imaging assessment methods primarily rely on X-rays, CT scans, or MRI to detect changes in bone volume and morphology at the defect margins. These methods lack sensitivity to early molecular-level changes in skull regeneration and often fail to provide reliable predictive information before significant changes in cell activity occur. For pediatric patients in their rapid growth phase, skull growth rate is closely related to fluctuations in molecular signals. Relying solely on imaging indicators or clinical observation can easily lead to delayed or premature timing assessments, thus affecting the quality of bone graft fusion and the effectiveness of skull morphological reconstruction.

[0038] The proposed strategy for the combined detection of FAK, Twist1, and their downstream soluble bone growth factors (BMP-2 and TGF-β1) combines macroscopic characterization of skull growth with microscopic molecular mechanisms, enabling the capture of the activation status of osteogenic-related signaling pathways. FAK, as a core kinase in cell adhesion and mechanosensitive sensing, plays a pivotal role in osteoblast attachment to the dura mater surface, sensing the external mechanical environment, and initiating signal transduction. Twist1 regulates the differentiation of osteoblast precursor cells into osteoblasts during skull development, and its transcriptional activity directly affects the expression levels of BMP-2 and TGF-β1, both of which are key molecules promoting bone matrix formation and mineralization.

[0039] During the testing process, by collecting dura mater tissue or blood samples and measuring the mRNA and protein levels of the aforementioned biomarkers, molecular information on bone repair potential can be obtained in the early stages of bone formation. This molecular testing result can predict the rate and trend of skull growth before significant bone increase is observed on imaging, thus providing a more early and accurate reference for surgical decisions. Particularly in pediatric skull defect repair, this method can avoid secondary surgeries or repair failures due to inappropriate surgical timing.

[0040] In determining the timing of surgery, a significant increase in the levels of FAK, Twist1, and their downstream factors indicates that osteoblasts are highly active in the defect margin area, accelerating bone matrix deposition and mineralization. Repairing at this time can achieve ideal osseointegration. Conversely, when the levels of these molecules are low or show no obvious upward trend, it suggests insufficient osteogenic activity. Hasty repair may lead to poor bone healing or implant integration failure, requiring continued observation and adjustment of the intervention strategy.

[0041] In terms of postoperative management, dynamic monitoring of biomarkers can serve as molecular indicators for assessing the quality of bone repair and the risk of complications. After the repair surgery, if FAK, Twist1, BMP-2, and TGF-β1 are consistently highly expressed, it indicates that the bone remodeling process in the implantation area is successful and the repair material is firmly integrated with the host bone. Conversely, if the biomarker levels decrease or remain below the normal reference range for an extended period, it may indicate accelerated bone resorption, implant loosening, or the presence of a chronic inflammatory response, requiring timely imaging follow-up or secondary intervention.

[0042] The advantage of this method in industrial applications lies in its seamless integration with existing molecular detection platforms and automated quantitative equipment. The detection process is highly standardized and reproducible, making it suitable for large-scale clinical application. By incorporating molecular marker detection into the decision-making process for cranioplasty, the accuracy of surgical timing can be significantly improved, the incidence of postoperative complications reduced, and quantifiable biological evidence provided for precision medicine and personalized treatment, thus creating a new diagnostic and treatment paradigm in the fields of craniofacial surgery and bone regeneration medicine.

[0043] The rapid growth marker of the skull provided in this embodiment of the invention includes: FAK, Twist1, and soluble bone growth factor regulated by Twist1, wherein the soluble bone growth factor is selected from at least one of bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β1 (TGF-β1).

[0044] like Figure 1 As shown in the embodiment of the present invention, an application method of a rapid skull growth marker is provided:

[0045] S101, Collect dura mater tissue and / or blood samples from pediatric patients with skull defects;

[0046] S102, detect the mRNA and / or protein expression levels of FAK, Twist1, BMP-2 and TGF-β1 in the sample;

[0047] S103, assess the patient's skull growth and development status based on the expression level of markers to determine the timing of cranioplasty;

[0048] S104, Perform cranial defect repair surgery at the appropriate time;

[0049] S105, postoperative marker expression levels are monitored regularly to assess surgical outcomes and patient prognosis.

[0050] The working principle of this biomarker system is based on the dynamic monitoring of molecular signaling pathways related to skull growth. FAK (focal adhesion kinase) plays a crucial role in cell adhesion, migration, and bone tissue biomechanical signal transduction; its activation promotes the directed migration of osteoblasts and bone matrix deposition in defect areas. Twist1, as a transcription factor, regulates the expression of downstream bone growth-related genes, particularly promoting the synthesis and secretion of key soluble factors BMP-2 and TGF-β1 during bone formation, thereby driving osteoblast differentiation and bone matrix mineralization. By combining these three signaling molecules as biomarkers, the molecular activity level of skull regeneration and repair can be comprehensively reflected.

[0051] During application, dura mater tissue and / or blood samples are used as detection sources to reflect the molecular signal status in the patient's skull growth environment in real time. mRNA level detection can reveal changes in gene transcriptional activity, while protein level detection directly reflects the strength of molecular executive function. When the expression levels of FAK, Twist1, and their regulated BMP-2 and TGF-β1 are high, it indicates that skull regeneration is in an active phase, suitable for defect repair to achieve the best fusion effect; if the expression levels are low, it indicates insufficient bone growth potential, and premature repair may lead to poor integration of the implant material with the host bone.

[0052] During postoperative follow-up, continuous monitoring of changes in the expression of these biomarkers can be used to assess the surgical repair effect and the progress of bone tissue remodeling. If the postoperative biomarker levels remain stable or gradually increase, it indicates good osteogenic activity in the repaired area; if the levels decrease or remain below normal for a long period, it may indicate insufficient bone regeneration or risks such as implant rejection or bone resorption. This provides a molecular basis for clinical intervention, enabling individualized selection of surgical timing and postoperative management.

[0053] The detection sample provided in this embodiment of the invention:

[0054] Histological and molecular biological techniques were used to test the samples;

[0055] Histological techniques: Immunohistochemical staining was used to observe the localization and expression of FAK and Twist1 in the dura mater tissue;

[0056] Molecular biology techniques: real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the mRNA and protein expression levels of FAK, Twist1, and related bone growth factors (BMP-2 and TGF-β1) in dura mater tissue and blood samples, respectively.

[0057] Animal model testing and in vitro cell culture testing.

[0058] like Figure 2 As shown, the model animal detection provided in this embodiment of the invention:

[0059] S201, establish an animal model of pediatric skull development and defect repair, and collect dura mater tissue and blood samples from animals at different developmental stages and repair time points;

[0060] S202 uses the same detection technology as clinical samples to detect biomarkers in animal models to verify their expression patterns and their correlation with skull growth and development.

[0061] The in vitro cell culture detection provided in this embodiment of the invention involves culturing dura mater cells in vitro, simulating intracranial pressure changes by applying different pressure stimuli, and using the aforementioned molecular biology techniques to detect changes in the expression of FAK, Twist1, and related bone growth factors in the cells before and after pressure stimulation, thereby further clarifying the regulatory role of the pressure / dura mater FAK-Twist1 pathway on biomarker expression.

[0062] The postoperative periodic monitoring provided in this embodiment of the invention involves periodically collecting blood samples from patients after cranioplasty to detect the expression levels of biomarkers, thereby monitoring the growth and development of the skull and the surgical outcome. A gradual increase in biomarker expression levels after surgery indicates good skull growth and recovery; conversely, persistently abnormal biomarker expression levels or a declining trend may indicate poor surgical outcomes or complications, requiring timely and appropriate treatment.

[0063] like Figure 3 As shown, an embodiment of the present invention provides a rapid skull growth marker application system comprising:

[0064] The sample collection module is used to collect dura mater tissue and / or blood samples from pediatric patients with skull defects.

[0065] The sample detection module is used to detect the mRNA and / or protein expression levels of FAK, Twist1, BMP-2 and TGF-β1 in the sample;

[0066] The assessment module is used to evaluate the patient's skull growth and development status based on the expression levels of biomarkers, and to determine the timing of cranioplasty.

[0067] Repair module, used to perform cranial defect repair surgery at the appropriate time;

[0068] The postoperative monitoring module is used to periodically monitor biomarker expression levels after surgery to assess surgical outcomes and patient prognosis.

[0069] Example 1: Detection of rapid skull growth markers in clinical samples

[0070] 1. Sample Collection: Twenty children with skull defects were selected as the case group, and ten children without skull defects who required craniotomy for other reasons were selected as the control group. During the surgery, dura mater tissue was collected from both the case group and the control group, and 5 ml of venous blood was collected from all children and placed in anticoagulant tubes for later use.

[0071] 2. RNA extraction and cDNA synthesis: Total RNA was extracted from dura mater tissue and blood leukocytes using Trizol reagent, and the RNA was reverse transcribed into cDNA using a reverse transcription kit.

[0072] 3. qRT-PCR Detection: Specific primers for FAK, Twist1, BMP-2, and TGF-β1 were designed, with β-actin as an internal reference gene. The expression levels of each biomarker mRNA were detected using qRT-PCR. The reaction system consisted of 20 μl of 2×SYBR Green PCR Master Mix (10 μl), forward and reverse primers (10 μM) (0.5 μl each), cDNA template (2 μl), and ddH2O (7 μl). The reaction conditions were: 95℃ pre-denaturation for 5 min; 95℃ denaturation for 10 s; 60℃ annealing and extension for 30 s, for a total of 40 cycles. The relative expression levels of each biomarker were calculated using the 2-ΔΔCt method.

[0073] 4. Western blot analysis: Total protein was extracted from dura mater tissue, and protein concentration was determined using a BCA protein quantification kit. Equal amounts of protein were subjected to SDS-PAGE gel electrophoresis and then transferred to a PVDF membrane. After blocking with 5% skim milk for 1 hour, primary antibodies (FAK, Twist1, BMP-2, TGF-β1, and β-actin antibodies) were added and incubated overnight at 4°C. After washing with TBST, secondary antibody was added and incubated at room temperature for 1 hour. Finally, the membrane was developed with ECL chemiluminescence reagent, and the bands were analyzed using ImageJ software for grayscale value analysis.

[0074] 5. Results Analysis: Compared with the control group, the expression levels of FAK, Twist1, BMP-2 and TGF-β1 in dura mater tissue and blood were significantly different in the case group (P < 0.05), and the expression levels of the markers also differed among patients in different growth and development stages, suggesting that these markers may serve as potential markers of rapid skull growth in children.

[0075] Example 2: Validation of biomarkers for rapid skull growth in animal models

[0076] 1. Animal model establishment: Newborn SD rats were randomly divided into a normal control group and a skull defect model group. Rats in the model group underwent skull defect surgery on day 7 after birth to create a circular skull defect approximately 3 mm in diameter.

[0077] 2. Sample Collection and Detection: Dura mater tissue and blood samples were collected from rats in the model group and control group on postoperative days 3, 7, 14, and 21. The expression levels of FAK, Twist1, BMP-2, and TGF-β1 were detected using the same qRT-PCR and Western blot techniques as in Example 1.

[0078] 3. Results Analysis: For example... Figure 4 As shown, with the passage of time after surgery, the expression levels of biomarkers in the dura mater and blood of rats in the model group exhibited a trend of first increasing and then decreasing, and were closely related to the repair and growth stages of skull defects. In the early stage of skull defect repair, biomarker expression levels significantly increased, indicating that the skull was in a rapid growth and repair phase; as repair was completed, biomarker expression levels gradually decreased. In the control group, biomarker expression levels remained relatively stable, further validating the correlation between these biomarkers and the growth and development and defect repair of pediatric skulls.

[0079] Example 3: Regulatory effect of the pressure / dura mater FAK-Twist1 pathway on biomarkers in in vitro cell culture

[0080] 1. Cell Culture and Pressure Stimulation: Rat dura mater cells were cultured in vitro. When the cell confluence reached 80%-90%, they were divided into a control group and different pressure stimulation groups (5 mmHg, 10 mmHg, 15 mmHg, 20 mmHg). A specially designed pressure loading device was used to apply the corresponding pressure stimulation to the cells for 24 hours.

[0081] 2. Biomarker detection: After the stress stimulation ended, cells were collected, and total RNA and total protein were extracted. The expression levels of FAK, Twist1, BMP-2 and TGF-β1 were detected by qRT-PCR and Western blot.

[0082] 3. Pathway Inhibition Assay: One hour before stress stimulation, the FAK-specific inhibitor PF-573228 (10 μM) was added to cells, followed by a 15 mmHg stress stimulation for 24 hours. Changes in biomarker expression after FAK activity inhibition were detected to verify the regulatory role of the FAK-Twist1 pathway on biomarkers.

[0083] 4. Results Analysis: For example... Figure 5As shown, with increasing stress intensity, the expression levels of FAK, Twist1, BMP-2, and TGF-β1 in dura mater cells gradually increased in a dose-dependent manner. After using a FAK inhibitor, the expression levels of Twist1 and its regulated bone growth factor significantly decreased, indicating that stress regulates the expression of these markers through the FAK-Twist1 pathway. This further supports the theoretical hypothesis that "stress / dura mater FAK-Twist1 pathway regulates developmental skull growth."

[0084] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications, equivalent substitutions, and improvements made by those skilled in the art within the scope of the technology disclosed in the present invention, and within the spirit and principles of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A biomarker composition for assessing the rapid growth status of a child's skull, characterized in that, include: The bone growth factor is selected from at least one of bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β1 (TGF-β1).

2. A method for assessing the rapid growth status of the skull based on the marker described in claim 1, characterized in that, Includes the following steps: Step 1: Collect dura mater tissue samples and / or blood samples from pediatric patients with skull defects; Step 2: The mRNA and / or protein expression levels of FAK, Twist1, BMP-2 and TGF-β1 in the sample were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot. Step 3: Assess the growth and development status of the skull based on the test results, and determine the timing of skull defect repair surgery accordingly.

3. The method as described in claim 2, characterized in that, Further includes: Blood samples were collected from patients regularly after cranioplasty to detect marker expression levels, monitor skull growth and recovery, and assess surgical outcomes.

4. The method as described in any one of claims 2 or 3, characterized in that, The detection further includes using immunohistochemical staining to observe the localization and expression of FAK and Twist1 proteins in the dura mater tissue.

5. The method as described in claim 4, characterized in that, Using an animal model of pediatric skull development and defect repair, dura mater and blood samples were collected at different developmental stages and repair time points to detect the expression levels of biomarkers and verify their correlation with skull growth.

6. The method as described in claim 5, characterized in that, By culturing dura mater cells in vitro and applying different pressure stimuli to simulate intracranial pressure changes, the expression changes of FAK, Twist1, and soluble bone growth factor were detected, and the regulatory effect of pressure stimulation on the expression of biomarkers was analyzed.

7. The method as described in claim 6, characterized in that, When in vitro pressure stimulation led to upregulation of FAK and Twist1 expression, simultaneous upregulation of BMP-2 and / or TGF-β1 expression was observed, suggesting the important role of the pressure / dura mater FAK-Twist1 pathway in the regulation of rapid skull growth.

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