Biomedical Chemistry: Research and Methods 2025, 8(2), e00262

ON THE QUESTION OF THE MOLECULAR AND GENETIC MECHANISMS BY WHICH BONE TISSUE OSTEOBLASTS INTERACT WITH BIOLOGICAL MATERIALS DURING OSTEOPLASTY

T.N. Medvedeva*, V.V. Rossinskaya, L.N. Kulagina, L.T. Volova

Samara State Medical University, Biotech Research Institute, 89 Chapaevskaya str,. Samara, 443079 Russia; *e-mail: tatjana.medv@rambler.ru

Keywords: osteoblasts; cell adhesion; activation of reparative processes; signaling pathways and enzymatic reaction cascades

DOI:10.18097/BMCRM00262

The whole version of this paper is available in Russian.

The article herein sets out to show the molecular and genetic mechanisms underpinning regenerative processes in bone tissue during the implantation of biological materials. The adhesion of osteoblasts to biological materials is a pivotal step in the transfer of physicochemical signals from biomaterials to osteoblasts. Initially, bone tissue cells interact with the biological material indirectly, through specific extracellular matrix proteins, especially vitronectin, fibronectin, and type I collagen. During the period preceding direct contact of osteoblasts with the implant, it is possible for blood proteins to be absorbed on the surface of the biological material in few seconds. Exactly the formation of a "protein layer" on the implants has been demonstrated to favour the adhesion of osteoblasts. The process of adhesion of osteoblasts to blood proteins is facilitated by a specific sequence, RGD, a tripeptide consisting of the amino acids Arg, Gly and Asp. This sequence is characteristic of vitronectin, fibronectin, type I collagen, osteopontin, bone sialoprotein and thrombospondin. Integrin-related signalling pathways can be categorised into two distinct types: those that are contingent on the Src-FAK complex and those that are not. It has been established that the phosphorylation of FAK at various sites can trigger multiple signalling pathways, including the PI3K/Akt/mTOR pathway, the Ras/MAPK/ERK1/2 pathway, and the p130Cas-RhoA GTPase pathway. For signalling pathways whose action is not contingent on the Src-FAK complex, integrin-linked kinase (ILK) is a pivotal regulatory factor. Among other significant cell membrane proteins, cadherins have been demonstrated to function as signal transduction molecules, contributing to the regulation of critical cellular activities. Consequently, in addition to the physical attachment of osteoblasts to biomaterials, cell adhesion leads to the activation of several signalling pathways, among which integrin- and cadherin-related signalling pathways are the most significant.

Figure 1. MSC differentiation. The possible differentiation ways of mesenchymal stem cells. Development of osteoblasts and the appearance of osteocytes ([23]).

Figure 2. Osteoblastic cell adhesion proteins. The ECM proteins mainly composed of collagen I, vitronectin and fibronectin shared with the specific RGD sequence. Integrins and cadherins are transmembrane proteins with an extracellular domain binding ligands as well as an intracellular domain connected with cytoskeletal proteins. Cytoskeletal proteins, including FAK, talins, vinculins, β-catenin and actins, are a collection of interconnected molecules contribute together to the formation of focal adhesions (adapted from[4]).

Figure 3. Conventional osteogenic differentiation pathways. Cartoon showing the two classical osteogenic differentiation pathways of MSCs/preosteoblasts, i.e., the bone morphogenic pathway and the Wnt/β-catenin pathway. BMPRs—BMP receptors; BAMBI—BMP and activin membrane-bound inhibitor homolog; CRIM1—cysteine-rich motor neuron 1 protein; SMAD—small mothers against decapentaplegic; DKK1—Dickkopf-related protein 1; sFRP2—secreted frizzled-related protein 2; Kremen—Kringle domain-containing transmembrane protein; LRP—Low Density Lipoprotein Receptor-Related Protein; GSK—glycogen synthase kinase; CKIα—casein kinase Iα; APC—adenomatous polyposis coli; TCF/LEF—T-cell factor/lymphoid enhancer-binding factor ([23]). In the nucleus, β-catenin activates transcription factors (T-cell factor/lymphoid factor lead to activation of target gene expression).

FUNDING

No external funding.

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