Name: Video: Murine Orthodontic Tooth Movement (OTM) Model
Uploaded: 2023-07-21T12:20:00
Description: 247 Views. Murine Orthodontic Tooth Movement (OTM) Model

murine orthodontic tooth movement (otm) model

Analyzing Alveolar Bone Remodeling to Explore Skeletal Mechanical Biology

It is generally known that bone is under constant reconstruction throughout life, in response to mechanical forces according to Wolff&#39;s law1,2. Appropriate mechanical stimulation, such as gravity and daily exercise, maintains bone mass and strength and prevents bone loss by stimulating both osteoblasts and osteoclasts. Osteoclasts, responsible for bone resorption3,4,5,6,7, and osteoblasts, responsible for bone formation8,9,10, maintain bone homeostasis and function jointly in the biological process of bone remodeling. In contrast, in the absence of loading stimuli, as in astronauts under long-term microgravity, bones suffer 10% bone mineral density loss, thus increasing the risk of osteoporosis11,12. Furthermore, noninvasive and convenient mechanical therapies, including orthodontics and distraction osteogenesis, have emerged as treatments for bone diseases13,14. All these have shown that mechanical force plays a critical role in maintaining bone quality and quantity. Recent studies generally analyzed bone remodeling in response to mechanical loading using time-consuming models such as running wheel and tail suspension tests, which usually took 4 weeks or more to simulate force loading or unloading15,16. Therefore, there is demand for a convenient and efficient animal model for studying bone remodeling driven by force loading.
The alveolar bone is the most active in terms of bone remodeling, with a high turnover rate17. Orthodontic tooth movement (OTM), a common treatment for malocclusion, is an artificial process of alveolar bone remodeling in response to mechanical force. However, OTM, which induces rapid bone remodeling18, is also a time-saving way to study the effects of mechanical force on bone remodeling compared with other models with a long experimental period. Therefore, OTM is an ideal model to study bone remodeling under mechanical stimuli. It is noteworthy that the mechanism of alveolar bone remodeling is often time-sensitive, and it is necessary to observe the changes in alveolar bone remodeling at certain time points after modeling. With the dual advantages of temporal and spatial control of DNA recombination and tissue specificity, an inducible conditional gene knockout mouse model is a suitable choice for OTM studies.
Conventionally, OTM-mediated alveolar bone remodeling has been divided into tension zones involving bone formation and pressure zones involving bone resorption19,20,21, which is more detailed but difficult to regulate. Furthermore, Yuri et al. reported that the time of bone formation in OTM differed on the tension and compression sides22. In addition, a previous study had demonstrated that the first molar could initiate wide remodeling of the maxillary alveolar bone under orthodontic force, which was not constrained to the tension and pressure zones23. Therefore, we selected the area located within three roots of M1 in the cross-section of the maxillary bone as the region of interest (ROI) and described methods to assess the activity of osteoblasts and osteoclasts in the same area to evaluate alveolar bone remodeling under OTM.
As a nuclear transcription factor, signal transducer and activator of transcription 3 (STAT3) has been proven critical in bone homeostasis24,25. Previous studies have reported low bone mineral density and recurrent pathological fractures in Stat3-mutant mice26,27. Our previous study demonstrated that deletion of Stat3 in Osx+ osteoblasts caused craniofacial malformation and osteoporosis, as well as spontaneous bone fracture28. Recently, we provided in vivo evidence with an inducible osteoblast-specific Stat3 deletion mouse model (Col1&#945;2CreERT2; Stat3fl/fl, hereafter called Stat3Col1&#945;2ERT2) that STAT3 is critical in mediating the effects of orthodontic force driving alveolar bone remodeling29. In this study, we provide methods and protocols for using inducible osteoblast lineage-specific Stat3 knockout mice to study bone remodeling under orthodontic force and describe methods for analyzing alveolar bone remodeling during OTM, thus shedding light on skeletal mechanical biology.

Author Spotlight: Comparing Alveolar and Long Bone Remodeling to Explore OTM Model Potential 

Using Inducible Osteoblastic Lineage-Specific Stat3 Knockout Mice to Study Alveolar Bone Remodeling During Orthodontic Tooth Movement

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Murine Orthodontic Tooth Movement (OTM) Model  

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247 Views. Murine Orthodontic Tooth Movement (OTM) Model

Video: Murine Orthodontic Tooth Movement (OTM) Model  

The alveolar bone, with a high turnover rate, is the most actively-remodeling bone in the body. Orthodontic tooth movement (OTM) is a common artificial process of alveolar bone remodeling in response to mechanical force, but the underlying mechanism remains elusive. Previous studies have been unable to reveal the precise mechanism of bone remodeling in any time and space due to animal model-related restrictions. The signal transducer and activator of transcription 3 (STAT3) is important in bone metabolism, but its role in osteoblasts during OTM is unclear. To provide in vivo evidence that STAT3 participates in OTM at specific time points and in particular cells during OTM, we generated a tamoxifen-inducible osteoblast lineage-specific Stat3 knockout mouse model, applied orthodontic force, and analyzed the alveolar bone phenotype. 
Micro-computed tomography (Micro-CT) and stereo microscopy were used to access OTM distance. Histological analysis selected the area located within three roots of the first molar (M1) in the cross-section of the maxillary bone as the region of interest (ROI) to evaluate the metabolic activity of osteoblasts and osteoclasts, indicating the effect of orthodontic force on alveolar bone. In short, we provide a protocol for using inducible osteoblast lineage-specific Stat3 knockout mice to study bone remodeling under orthodontic force and describe methods for analyzing alveolar bone remodeling during OTM, thus shedding new light on skeletal mechanical biology.

This study provides a protocol for using inducible osteoblast lineage-specific Stat3 knockout mice to study bone remodeling under orthodontic force and describes methods for analyzing alveolar bone remodeling during orthodontic tooth movement, thus shedding light on skeletal mechanical biology.

The alveolar bone, with a high turnover rate, is the most actively-remodeling bone in the body. Orthodontic tooth movement (OTM) is a common artificial ...