Effects of Extracellular Osteoanabolic Agents on the Endogenous Response of Osteoblastic Cells

Abstract

The complex multidimensional skeletal organization can adapt its structure in accordance with external contexts, demonstrating excellent self-renewal capacity. Thus, optimal extracellular environmental properties are critical for bone regeneration and inextricably linked to the mechanical and biological states of bone. It is interesting to note that the microstructure of bone depends not only on genetic determinants (which control the bone remodeling loop through autocrine and paracrine signals) but also, more importantly, on the continuous response of cells to external mechanical cues. In particular, bone cells sense mechanical signals such as shear, tensile, loading and vibration, and once activated, they react by regulating bone anabolism. Although several specific surrounding conditions needed for osteoblast cells to specifically augment bone formation have been empirically discovered, most of the underlying biomechanical cellular processes underneath remain largely unknown. Nevertheless, exogenous stimuli of endogenous osteogenesis can be applied to promote the mineral apposition rate, bone formation, bone mass and bone strength, as well as expediting fracture repair and bone regeneration. The following review summarizes the latest studies related to the proliferation and differentiation of osteoblastic cells, enhanced by mechanical forces or supplemental signaling factors (such as trace metals, nutraceuticals, vitamins and exosomes), providing a thorough overview of the exogenous osteogenic agents which can be exploited to modulate and influence the mechanically induced anabolism of bone. Furthermore, this review aims to discuss the emerging role of extracellular stimuli in skeletal metabolism as well as their potential roles and provide new perspectives for the treatment of bone disorders.

Cyclic Stretch-Induced Mechanical Stress Applied at 1 Hz Frequency Can Alter the Metastatic Potential Properties of SAOS-2 Osteosarcoma Cells

“…The following supporting information can be downloaded at https: //www.mdpi.com/article/10.3390/ijms24097686/s1. References [8,25,53,[57][58][59][60][61] are cited in the supplementary materials.…”

“…The application of loading forces (e.g., cyclic tensile forces) has been reported to promote anabolism by stimulating osteogenesis both in vitro and in vivo [4][5][6]. Interestingly, mechanical factors are essential not only for the well-known preservation of bone quality and quantity but also because they contribute to the development of cancer [7][8][9][10]. Increasing evidence suggests that environmental mechanics has a significant impact on gene expression, cell fate, and function and ultimately gives rise to modifications of the malignancy of osteosarcoma [7,11,12].…”

Multi-Anticancer Activities of Phytoestrogens in Human Osteosarcoma

“…In both primary bone cancer and bone metastases, the bone remodeling process creates a favorable environment for tumor establishment and progression. Osteoblasts and osteoclasts are the primary regulators of bone metabolism [105]. Specifically, osteoblasts secrete multiple components of ECM and MMPs in the OS niche, which are rich promoters of OS development.…”

Mechano-induced cell metabolism disrupts the oxidative stress homeostasis of SAOS-2 osteosarcoma cells

“…The human body is constantly affected by physical forces which change molecular properties determining how cells behave. Over the past 20 years, there has been extensive research on mechanosensing and mechanotransduction, particularly in adherent cells ( Michaletti et al, 2017 ; Mohammed et al, 2019 ; Alloisio et al, 2021 ). These processes are now recognized to play vital roles in numerous essential cellular functions, including adhesion and proliferation, mitosis, motility, and apoptosis ( Holle and Engler, 2011 ; Gioia et al, 2018 ; Alloisio et al, 2021 ; Harris and Hawkins, 2022 ).…”

“…Over the past 20 years, there has been extensive research on mechanosensing and mechanotransduction, particularly in adherent cells ( Michaletti et al, 2017 ; Mohammed et al, 2019 ; Alloisio et al, 2021 ). These processes are now recognized to play vital roles in numerous essential cellular functions, including adhesion and proliferation, mitosis, motility, and apoptosis ( Holle and Engler, 2011 ; Gioia et al, 2018 ; Alloisio et al, 2021 ; Harris and Hawkins, 2022 ). Similarly, cancer cells exert forces to facilitate their spread to other parts of the body while consuming ATP.…”