Introduction:
Osteoblasts are one of the critical cells in the process of bone remodeling and are one of the components of the bone multicellular units. Mechanotransduction refers to the process by which responsiveness to mechanical stimuli is converted into biochemical signals, which are then coordinated into cellular responses. The article discusses the mechanotransduction of osteoblasts and their role in treating various bone pathophysiology in detail.
What Is the Role of Osteoblasts?
Osteoblasts are the bone-forming cells that originate from the mesenchymal cells (cells that are embryologically developed from the middle germ layer) of the non-hematopoietic parts of the bone marrow (spongy tissue located in the center of the bone), which are a group of stem cells that has the potential to differentiate into bone-forming cells. These mesenchymal stem cells (MSC) are also called skeletal stem cells (SSC) and multipotent mesenchymal stromal cells (MMSC). Mesenchymal stromal cells refer to the cells that have the potential to self-renew and can differentiate into other types of cells. Osteoblasts are the primary components of the bone multicellular unit (BMU).
Microarchitecture of the bone is based on processes, namely the bone remodeling process, osteogenesis, and bone modeling process. The bone turnover is brought about by the bone remodeling process (renewing the old bone by the formation of new bone), which involves the resorption of the functioning mineralized bone matrix, which is facilitated by osteoclasts (bone-resorbing cells) and the formation of new bone on the surface of the bone which is facilitated by the osteoblasts (bone-forming cells). This process is essential to maintain skeletal integrity and the metabolic levels of calcium and phosphorus in the skeletal system.
What Is Mechanotransduction?
Mechanotransduction involves the set of mechanisms that permits the cell to convert the mechanical stimulus into biochemical activity, leading to changes in intercellular components such as activation of signaling pathways, ion concentration, and transcription regulation. The physiological process of bone is generally regulated by the ability of the involved skeletal cells to perceive and integrate mechanical energy into a cascade of biochemical and structural changes in the cells. The cellular response increases bone loss while not being used longer and reduces the bone loss while loading force.
How Do Mechanical Signals Trigger Osteoblast Differentiation?
Bone tissues such as osteoblasts, osteoclasts, and osteoprogenitor cells are all sensitive to mechanical stress stimulation. Literature suggests that loss of mechanical stress can result in bone microstructure degeneration, bone mass loss, and metabolic disorders and ultimately result in osteoporosis (a disease that develops when bone mass and bone mineral density decrease).
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Lack of mechanical stress in cases of bed rest, reduced exercises, limb cast fixation, and weightlessness of astronauts in space can cause significant loss of bone mass.
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Whereas increased mechanical load by exercising has been shown to restore bone mass and reverse the effects.
Mechanotransduction of osteoblasts is a complex but precise process between the bone-forming cells and the microenvironment and between the mechanical sensors of each cell. The mechanical sensors that are proven to regulate intercellular signaling pathways include integrins, ion channels, focal adhesion kinase, gap junction proteins, and primary cilia. Studies have shown that mechanical stress stimulation can reduce osteoclast activity, inhibiting bone resorption and promoting and facilitating osteoblasts' differentiation and bone-forming properties.
What Are the Biochemical Changes in Osteoblast?
A. Ion Channels: Ion channels are transmembrane proteins on the plasma membrane. These proteins arrange themselves to transport ions across the plasma membrane to regulate cell membrane potential.
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Mechanical stimulation has been shown to activate calcium channels on the plasma membrane to regulate the transport of calcium ions into the cells, increasing the calcium concentration intracellular and promoting increased bone mass.
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Piezo 1 channel located on the plasma membrane is one of the important mechanosensitive ion channels through which osteoblasts show responsive changes to the mechanical load. Studies show that peizo1 deficiency in osteoblast increases bone resorption and promotes osteoporosis.
B. Cytoskeleton: Cytoskeleton is a complex structure in the cytoplasm of all cells responsible for maintaining a cell's shape and internal organization. They are primarily composed of protein fiber and are highly non-linear. Cytoskeleton enables the cells to sense and detect deformations and changes and maintain the tight adhesion between the cells and the extracellular matrix.
C. Integrins: Integrins are the membrane-bound proteins that are found to be the essential components of the 'ligand-integrin cytoskeleton' linkage, a crucial two-way mechanotransductive process.
D. Primary Cilia: Human cells have hair-like structures called cilia that protrude from their surfaces and detect external physical forces. Recent studies show the function of primary cilia in regulating osteogenic mechanotransductive pathways. There is a statistically significant reduction in bone formation in reaction to mechanical loading when a gene that codes for the development of primary cilia is deleted.
What Are the Effects of Mechanical Stimulation?
Mechanotransduction of osteoblast is regulated by multiple signaling pathways such as the Wnt/β-catenin signaling pathway (responsible for handling key cellular functions such as cellular proliferation, differentiation, and migration), Notch signaling pathway (highly critical pathways responsible for regulating various cell processes in diseases), ERK5 signaling pathway, and Rhoa signaling pathway.
Mechanical stimulus induces stress, stimulating and transmitting the force to the bone cells. Mechanoreceptors of the cell membrane are activated by binding specific receptors to the ligands, which in turn triggers a cascade of signaling pathways and enhances the expression of target genes. The mechanical stimuli triggering the osteoblast differentiation include fluid flow, integrin stimulation, substrate strain, vibration, compression loading, and altered gravity.
What Is the Role of Mechanotransduction in Bone-Related Disease?
The skeletal system is designed to respond and adapt to mechanical loads. The direction of bone formation and resorption differs when the overloading increases or decreases. Some bone-related diseases, such as osteomalacia or rickets, show a reduction in bone mineralization. Other conditions, such as osteoarthritis or rheumatoid arthritis, occur due to adverse immune responses. However, most bone-related conditions disrupt the balance between osteoclastic and osteoblastic activity. The loss of balance may originate because of a genetic abnormality.
Osteoporosis: A bone disease with increased osteoclastic activity (increased bone resorption) and decreased osteoblastic activity. The primary goal of management in these conditions is to achieve a higher rate of osteoblastic activity than bone resorption. Mechanical stimulation can reverse the process by suppressing the formation of bone-resorbing cells.
Conclusion:
The responsiveness and adaptability of the skeletal system to various stimuli make the skeletal cells, such as osteoblasts, osteoclasts, osteocytes, and osteoprogenitor cells, maintain the dynamic balance of the bone architecture. The therapeutic approach of mechanical stimulation in bone disorders needs further research and investigation.
