Devices and methods for modeling rat temporomandibular joint osteoarthritis

Abstract

A method for modeling temporomandibular joint osteoarthritis, 6-week-old rats are selected, the rats are confirmed to have entered an anesthetized state before surgery, the rat's mandibular incisors are first checked and confirmed to be normal, the first arm of the device is sleeved on one side of the mandibular incisor, and the palatal side of the maxillary incisor is made to touch the slope surface of the second arm of the device, the device is checked and confirmed to not affect the rat's mandibular movement and occlusion, not significantly raise the bite, have no early contact, and the upper and lower jaw relationship is relatively stable; the device and the mandibular incisor sleeved with the device are fixed; then the rat is put back into the cage, and soft food or powdered feed is given after waking up; the device is removed after being fed for 8 weeks or more. It is verified that the condylar process of the rat changes significantly, the overall condylar process is significantly reduced, the subchondral bone is destroyed, and the expression of the cartilage matrix is also reduced. Thus, a TMJOA rat model exhibiting mandibular retrusion is formed.

Description

Technical Field

[0001] This invention relates to an animal model creation technique, and more particularly to a device and method for constructing an animal model of temporomandibular joint osteoarthritis. Background Technology

[0002] Osteoarthritis is a common chronic degenerative disease affecting joints throughout the body, primarily characterized by chondrocyte degeneration and subchondral bone sclerosis. The temporomandibular joint (TMJ) is the only joint in the maxillofacial region that is bilaterally involved and closely related to daily living functions such as chewing and speaking. It is also one of the common sites for osteoarthritis (OA). Temporomandibular joint osteoarthritis (TMJOA) can severely impact and reduce patients' quality of life.

[0003] Class II skeletal malocclusion is a common maxillofacial deformity in clinical practice, mainly characterized by relative maxillary protrusion and mandibular retrusion, often accompanied by deep overbite. Studies have shown that patients with Class II skeletal malocclusion have a higher rate of temporomandibular joint disorder, and a significantly increased probability of long-term condylar resorption and osteoarthritis. Therefore, the impact of abnormal occlusal relationships on the development of TMJOA has been a key research focus. Currently reported models of abnormal occlusal relationships include unilateral anterior crossbite (UAC), bilateral anterior elevation (BAE), mandibular deviation (MDO), double-inclined device (TIPD), posterior elevation model, and maxillary guide-induced condylar posterior displacement, etc.

[0004] Among the aforementioned models, the UAC model is currently the most commonly used to induce TMJOA. This model simulates mandibular protrusion, which is inconsistent with mandibular retrusion. In 1996, Desai et al. reported a maxillary anterior tooth device that, by installing a palatal blocking plate on the maxillary anterior teeth of animals, restricts mandibular protrusion, placing the condyle in a relatively posterior position and inducing functional posterior displacement of the condyle. This device can simulate Class II maxillary-mandibular relationships and significantly induce changes in condylar cartilage and the temporomandibular joint. However, this device is relatively complex to prepare, prone to falling off, and affects the normal movement trajectory of the mandible. Apart from the aforementioned palatal blocking plate on the maxillary anterior teeth, there are currently no other mandibular retraction devices installed on the mandibular anterior teeth of rats to simulate deep overbite, nor are there any reports of other mandibular retraction devices causing temporomandibular joint osteoarthritis. Summary of the Invention

[0005] One objective of this invention is to provide a modeling device for temporomandibular joint osteoarthritis, which is installed on the mandibular incisor of a rat to simulate mandibular retraction and deep overbite, thereby implementing TMJOA modeling in rats.

[0006] Another objective of this invention is to provide a modeling device for temporomandibular joint osteoarthritis, which has a simple structure and is easier to fit onto the mandibular incisors of rats to achieve a rat model of TMJOA.

[0007] Another object of the present invention is to provide a modeling device for temporomandibular joint osteoarthritis, which reduces the impact on the basic functional movement of the mandible of animals, especially on feeding.

[0008] Another objective of this invention is to provide a modeling method for temporomandibular joint osteoarthritis, which makes it easier to obtain a rat model of TMJOA and facilitates related animal experiments and clinical research.

[0009] A modeling device for temporomandibular joint osteoarthritis, including

[0010] The first arm is tubular and is fitted onto the rat's mandibular incisor on one side (i.e., the left or right side) so that the mandibular incisor is placed inside the tube.

[0011] The second arm, including the slope, abuts against the palatal side of the maxillary incisor;

[0012] The first and second arms are connected, forming a "V" shape.

[0013] The length of the first arm is 5mm ± 1mm, and the slope length of the second arm is 4mm ± 1mm.

[0014] The axis and slope of the first arm are 55°±5°, such as, but not limited to, 51°, 52°, 53°, 54°, 55°, 56°, 57°, 58°, 59° and 60°.

[0015] The device of the present invention can be made using a No. 25 milk tube to make the first arm and the second arm. After the first arm is completed, the second arm with a slope is bent at the required angle (and then the second arm with the slope is connected to the first arm).

[0016] The device of the present invention is installed in the oral cavity of a rat, causing the rat's mandible to be pushed back, increasing the distance from the labial side of the mandibular incisors to the palatal side of the maxillary incisors, increasing coverage, so that when the rat is at rest, the condyle is located in the posterior part of the glenoid fossa relative to the control group rats. When protruding, the rat needs to increase the distance of mandibular protrusion in order to make the cusps of the upper and lower jaws contact and perform the chewing function.

[0017] The device of the present invention is installed in the oral cavity of a rat. The anterior bevel of the device makes slight contact with the palatal surface of the maxillary incisor, without affecting the rat's mandibular movement and mouth closure, without significantly raising the occlusion, without premature contact, and with a relatively stable relationship between the upper and lower jaws.

[0018] The device of the present invention is easy to prepare, low in cost, and convenient for laboratory operation. It only takes 5 minutes from fitting the device to bonding and fixing it. After bonding, it is relatively stable in the rat's mouth with a low detachment rate. Moreover, after installing the device, it does not affect the basic functional movement of the mandible and has little impact on eating.

[0019] A modeling method for temporomandibular joint osteoarthritis includes:

[0020] Six-week-old rats (e.g., SD rats) were selected, and it was confirmed before surgery that the rats were under anesthesia (e.g., 1% pentobarbital anesthesia).

[0021] First, check and confirm that there are no abnormalities in the left (or right) mandibular incisors of the rat. Then, attach the first arm of the device of the present invention to the left (or right) mandibular incisors and make the palatal side of the maxillary incisors touch the slope of the second arm. Check and confirm that the device does not affect the rat's mandibular movement and mouth closure, does not significantly raise the bite, does not have premature contact, and the relationship between the upper and lower jaws is relatively stable.

[0022] Then, fix the device to one side (left or right) of the mandibular incisor, for example: bond the device to the mandibular incisor (left or right) with glass ionomer cement;

[0023] Next, put the rat back into the cage. After it wakes up, give it plenty of drinking water and soft or powdered food (during the rearing period, check daily whether the device has fallen off. If it has fallen off, re-attach it immediately. Also check the adjacent teeth regularly. If they have elongated and affect the bite, trim them).

[0024] After 8 weeks or more of postoperative care, the devices are removed, thus completing the TMJOA rat model.

[0025] Verification showed that at 8 weeks post-surgery, significant localized bone destruction of the condyle, thinning of the cartilage, and disordered chondrocyte layers were observed. At 12 weeks post-surgery, the morphology of the rat condyle was significantly altered, with an overall marked reduction in condyle size. Abnormal remodeling of the subchondral bone occurred in the TMJOA rat model, with roughening of the cartilage surface, disordered layer arrangement, and reduced expression of the cartilage matrix. This resulted in the formation of a TMJOA rat model characterized by mandibular retrusion. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of the modeling device for temporomandibular joint osteoarthritis of the present invention installed at an angle in the oral cavity of an SD rat;

[0027] Figure 2 This is a schematic diagram of the modeling device for temporomandibular joint osteoarthritis of the present invention installed at another angle in the oral cavity of an SD rat;

[0028] Figure 3 A photograph of the modeling device for temporomandibular joint osteoarthritis of the present invention after being installed in the oral cavity of an SD rat;

[0029] Figure 4 Images of the modeling device for temporomandibular joint osteoarthritis of the present invention after being installed in the oral cavity of SD rats for 8 weeks (8 weeks) and the control group were taken by in vivo X-ray.

[0030] Figure 5 Micro-CT images of the temporomandibular joint of each group of animals at 4 weeks (4w), 8 weeks (8w), and 12 weeks (12w);

[0031] Figure 6 Comparison of the jawbone morphology of the animal model obtained after 12 weeks (12 weeks) and the blank control animal after Micro-CT scanning and Mimics reconstruction.

[0032] Figure 7 The results of H&E staining of the temporomandibular joint condyle and articular disc tissues of each group of animals at 4 weeks (4w), 8 weeks (8w), and 12 weeks (12w);

[0033] Figure 8 Images of temporomandibular joint condyles and articular discs at 4 weeks (4w), 8 weeks (8w), and 12 weeks (12w) of each group of animals after Safranin-Fix-Green staining. Detailed Implementation

[0034] The technical solution of the present invention will be described in detail below with reference to the accompanying drawings. The embodiments of the present invention are only used to illustrate the technical solution of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solution of the invention without departing from the spirit and scope of the technical solution of the present invention, and all such modifications and substitutions should be covered within the scope of the claims of the present invention.

[0035] Figure 1 This is a schematic diagram showing the modeling device for temporomandibular joint osteoarthritis of the present invention installed at an angle in the mouth of a mouse. Figure 2 This is a schematic diagram showing the modeling device for temporomandibular joint osteoarthritis of the present invention installed at another angle in the mouth of a mouse. (See diagram below.) Figure 1 and Figure 2 As shown, the device used for modeling temporomandibular joint osteoarthritis in this embodiment includes a first arm 100 and a second arm 200.

[0036] The first arm 100 is made of a No. 25 milk cannula and is fitted onto the left mandibular incisor 310 of the mouse, placing the mandibular incisor within the cannula's cavity. The second arm 200 includes a slope 210 that abuts against the maxillary anterior tooth 320. The first arm 100 and the second arm 200 are connected, forming a "V" shape. In this embodiment, the length of the first arm 100 is 5mm ± 1mm, and the length of the slope 210 is 4mm ± 1mm. The axial direction of the first arm 100 and the slope 210 form an angle of 55° ± 5°, such as, but not limited to, 51°, 52°, 53°, 54°, 55°, 56°, 57°, 58°, 59°, and 60°.

[0037] Before establishing the TMJOA rat model, 6-week-old SPF-grade SD rats were purchased and acclimatized for one week. They were then anesthetized with 1% pentobarbital. After confirming anesthesia, the left mandibular anterior teeth were examined and found to be normal. The first arm 100 of the device in this embodiment was attached to the left mandibular incisor, and the palatal side of the maxillary incisor was made to touch the slope 210 of the second arm.

[0038] The device was inspected and confirmed to not affect the rat's mandibular movement or mouth closure, not significantly elevate the bite, not cause premature contact, and maintain a relatively stable maxillary-mandibular relationship. After confirming successful placement of the device, it was bonded to one mandibular incisor using glass ionomer cement. Once the adhesive was completely dry, the rat was returned to its cage.

[0039] After the rats are revived, they are given plenty of drinking water and soft or powdered feed. The device is checked daily to see if it has fallen off. If it does, it is reattached immediately. The adjacent teeth are checked regularly. If they elongate and affect the bite, they are trimmed. The TMJOA rat model is completed 8 weeks or more after the operation.

[0040] Rats with the device of this embodiment implanted in their oral cavity, such as Figure 3 As shown, the rat's mandible was pushed back, increasing the distance from the labial side of the mandibular incisor to the palatal side of the maxillary incisor, thus increasing the coverage. When the rat was at rest, the condyle was located in the posterior part of the glenoid fossa relative to the control group. When the mandible was extended forward, the rat needed to increase the distance of mandibular extension in order for the cusps of the upper and lower jaws to contact each other and perform the chewing function.

[0041] Rats without the device of this embodiment were used as the control group, and rats with the device of this embodiment were used as the experimental group. The temporomandibular joints of the two groups of rats were examined at different time points after surgery. See details. Figure 5 As shown, Micro-CT scans were performed on the jaw joints of the experimental group animals at 4, 8, and 12 weeks post-surgery to observe the images. Compared with the control group, abnormal subchondral bone remodeling was observed in rats 4 weeks after implantation of the device described in this embodiment, gradually worsening at 8 weeks and continuing until 12 weeks post-surgery. Goodbye Figure 6As shown, H&E staining results indicated that 4 weeks after rats were fitted with the device of this embodiment, some roughness and disordered layer arrangement appeared on the surface of the temporomandibular joint cartilage layer in the experimental group, persisting until 12 weeks. Safranin-Fix Green staining results showed that 4 weeks after rats were fitted with the device of this embodiment, compared with the control group, the expression of temporomandibular joint cartilage matrix in the experimental group rats was reduced, and the reduction of cartilage matrix became more significant with time. At 12 weeks, the degree of reduction in cartilage matrix expression was more severe compared with the control group. See details. Figure 7 .

[0042] In addition, at 12 weeks, compared with the control group, the morphology of the temporomandibular joint condyle of the experimental group rats was significantly changed, and the overall condyle was significantly smaller than that of the experimental group.

[0043] This demonstrates that the method in this embodiment successfully constructed a TMJOA rat model induced by posterior mandibular displacement, providing a good animal model guarantee for subsequent animal experiments and clinical studies related to temporomandibular joint osteoarthritis.

Claims

1. A modeling device for osteoarthritis of the temporomandibular joint, characterized in that Comprising a first arm, being tubular, sleeved on one side of the rat's lower incisor, so that the lower incisor is placed in the lumen; a second arm, comprising a slope, which is in contact with the upper incisor; the first arm and the second arm are connected, forming a "V" shape.

2. The modeling device for osteoarthritis of the temporomandibular joint according to claim 1, characterized in that the length of the first arm is 5mm±1mm.

3. The modeling device for osteoarthritis of the temporomandibular joint according to claim 1, characterized in that the length of the slope of the second arm is 4mm±1mm.

4. The modeling device for osteoarthritis of the temporomandibular joint according to claim 1, characterized in that the axial direction of the first arm and the slope form an angle of 55°±5°.

5. The modeling device for osteoarthritis of the temporomandibular joint according to claim 1, characterized in that the first arm is made of a 25-gauge teat cannula.

6. A method of modeling osteoarthritis of the temporomandibular joint, characterized in that comprising the following steps: selecting 6-week-old rats, confirming that the rats have entered the anesthetic state before surgery; firstly, checking and confirming that one side of the rat's lower incisor is normal, sleeving the first arm of the device of claim 1 on one side of the lower incisor, and making the palatal side of the upper incisor touch the slope of the second arm of the device of claim 1, checking and confirming that the arrangement of the device does not affect the movement of the rat's lower jaw and the closing of the mouth, does not significantly raise the bite, does not have early contact, and the relationship between the upper and lower jaws is relatively stable; then, bonding and fixing the device with the lower incisor sleeved with the device; next, putting the rat back into the cage, and after waking up, giving sufficient drinking water and soft or powdered feed; feeding for 8 weeks or more after surgery, and removing the device.

7. The method of modeling temporomandibular joint osteoarthritis according to claim 6, wherein bonding the device with the one side of the lower incisor sleeved with the device with glass ionomer cement.

8. The method of modeling temporomandibular joint osteoarthritis according to claim 6, wherein during the feeding period, checking daily whether the device falls off, and if it falls off, re-bonding it immediately.

9. The method of modeling temporomandibular joint osteoarthritis according to claim 6, wherein during the feeding period, regularly checking the adjacent teeth, and if the elongation affects the bite, trimming them.

10. The method of modeling temporomandibular joint osteoarthritis according to claim 6, wherein feeding for at least 8 weeks or more after surgery, and removing the device.

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