ABSTRACT
The "mechanostat" principle may be depicted as an oscillating signal of a signaling molecule, in which the amplitude, frequency, cumulative level, delay, and duration of the curve encode the information for concrete cellular responses and biological activities. When the oscillating signal is kept sustained (present delay), cell exit may be performed, whereas when the oscillating signal remains robust, cell proliferation may take place. B-catenin-Wnt signaling pathway has a key role in the differentiation of osteochondroprogenitor cells. Sustained downregulation of the ß-catenin-Wnt pathway forces osteochondroprogenitors to a chondrogenic fate instead of an osteoblastic one. Other signaling, for example, bone morphogenetic protein and Notch signaling pathways interact with the Wnt pathway. The crosstalk between biochemical and mechanical stimuli produces the final information that leads to the final cell fate decisions, through the "mechanostat" principle.
Subject(s)
Cell Differentiation/physiology , Chondrocytes/metabolism , Chondrogenesis/physiology , Models, Biological , Osteoblasts/metabolism , Wnt Signaling Pathway/physiology , Animals , Chondrocytes/cytology , Humans , Osteoblasts/cytologyABSTRACT
Recent literature provides us with the indication that the ratio of OPG/RANKL concentrations fluctuate in a non-linear (bell-shaped) mode, according to Frost's "mechanostat" theory, during the application of mechanical strain. A similar cellular signal transduction mechanism to mechanical loading, that may also regulate bone resorptive activities, has nowdays been proposed. Since the skeleton is considered to be an endocrine organ, as such, it may likewise be subject to hypothalamic control. This central regulatory system may continually modulate the adaptation of the bone homeostatic system to external challenges. The hypothalamic-pituitary-gonadal axis may play a role in the regulation of OPG/RANKL secretion. The "mechanostat" principle may well characterize the oscillatory properties of the signal transduction mechanism that controls hard tissue metabolism and includes biochemical apart from mechanical stimuli. J. Cell. Biochem. 118: 962-966, 2017. © 2016 Wiley Periodicals, Inc.
Subject(s)
Hypothalamo-Hypophyseal System/metabolism , Osteoprotegerin/metabolism , RANK Ligand/metabolism , Receptor Activator of Nuclear Factor-kappa B/metabolism , Animals , Gene Expression Regulation , Humans , Mechanical Phenomena , Signal TransductionABSTRACT
Frost's great interest to elucidate the principles of action underlying skeletal deformities, during, and after growth, urged him to undertake an extensive study of the mammalian skeleton. He suggested that survival of the skeleton (but also of other tissues, such as fibrous tissue, hyaline cartilage, fibrocartilage, cementum, or dentin) requires the functional coordination of modeling and remodeling. Modeling adapts bone to overloads, by enhancing additions of new bone and by changing bone architecture, and remodeling adapts bone to underloads by removing bone next to marrow and conserving normally used bone. There exists a mechanism that monitors bone metabolism (longitudinal growth, bone modeling, and remodeling activities) in relation to mechanical usage, the "mechanostat." Recent literature has presented new information regarding the physiological procedure of osteoclast and osteoblast activation. It has been understood that the OPG/RANKL/RANK proteinic system regulates bone metabolism by exerting biological effects on osteoblasts or osteoclasts. The same proteinic network, also regulates alveolar remodeling during tooth movement, as well as physiological root resorption and root resorption during orthodontic tooth movement. The aim of the present review is the presentation and evaluation of recent information in the field of osteoclast and osteoblast biology, as regards to the "mechanostat theory" of Frost. An attempt will be made to elucidate, whether recent data can support this remarkable theory and reveal the biological mechanisms behind it.
Subject(s)
Bone Remodeling/genetics , Mechanical Phenomena , Osteoblasts/metabolism , Animals , Humans , Hyaline Cartilage/growth & development , Hyaline Cartilage/metabolism , Osteoblasts/cytology , Osteoclasts/cytology , Osteoclasts/metabolism , Osteoprotegerin/genetics , Osteoprotegerin/metabolism , RANK Ligand/genetics , RANK Ligand/metabolism , Receptor Activator of Nuclear Factor-kappa B/genetics , Receptor Activator of Nuclear Factor-kappa B/metabolismABSTRACT
The aim of the present study was the determination of the levels of osteoprotegerin and soluble RANKL in blood serum and in gingival crevicular fluid relative to the degree of orthodontic root resorption in a rat model. Blood samples and gingival crevicular fluid were collected from fourteen 6-month-old male Wistar rats weighing 350-500 g. A 25-g closed orthodontic coil spring was inserted between each upper right first molar and the upper incisors. After 21 days of loading, both upper first molars (treated and control) were extracted and studied under microcomputed tomography scanning. Statistical analysis demonstrated a positive linear correlation between the initial concentration of RANKL in blood serum and the degree of root resorption. The ratio of the initial concentrations of osteoprotegerin to RANKL in blood serum proved to be an independent prognostic factor of the degree of root resorption. The initial concentration of RANKL in gingival crevicular fluid showed a negative correlation to the initial concentration of RANKL in blood serum and for a finite range of initial concentrations of osteoprotegerin in gingival crevicular fluid, the dental root seemed protected against extreme external root resorption. Finally, the concentration of osteoprotegerin in blood serum decreased significantly in cases of severe root resorption.
Subject(s)
Gingival Crevicular Fluid/chemistry , Osteoprotegerin/blood , RANK Ligand/blood , Root Resorption/classification , Tooth Movement Techniques , Animals , Disease Models, Animal , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Incisor/pathology , Male , Molar/pathology , Orthodontic Wires , Osteoprotegerin/analysis , RANK Ligand/analysis , Rats , Rats, Wistar , Root Resorption/blood , Root Resorption/metabolism , Stress, Mechanical , Tooth Movement Techniques/instrumentation , Tooth Root/pathology , X-Ray Microtomography/methodsABSTRACT
Odontoclastic root resorption is a significant clinical issue in relation to orthodontic tooth movement, and resorption of the roots of primary teeth is an intriguing biological phenomenon. The functional coordination of the OPG/RANKL/RANK system seems to contribute not only to alveolar remodeling, but also to resorption during orthodontic tooth movement and physiological root resorption. Serum OPG and s-RANKL are related to regulation of bone homeostasis by the OPG/RANKL/RANK system, and determination of their concentrations might be useful for predicting the rate of bone remodeling during orthodontic tooth movement, the net effect between bone remodeling and root resorption, and the degree of root resorption. It is therefore rational to speculate that a study of the levels of OPG and s-RANKL in blood and GCF, in relation to the degree of root resorption during orthodontic tooth movement, using healthy experimental animals and a carefully planned and organized experimental design, may be able to answer this intriguing question.
