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Expression Dynamics of Bone Homeostasis Genes in the Development of Aseptic Femoral Head Necrosis in Rats

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Abstract

The pathogenesis of some diseases is characterized by a dysregulation of bone homeostasis, which is accompanied by progressive osteodestruction. At the same time, an active investigation of the mechanisms leading to the shift in the balance of osteoreparative and osteoresorptive processes of osteogenesis is underway. The identification of molecular and cellular patterns affecting the timecourse of changes in bone metabolism is a significant challenge for a wide range of specialists. Such studies allow improved algorithms to be proposed for targeted therapeutic impacts on key pathogenetic links of osteodestruction. Here, we analyzed the expression of genes involved in maintaining bone homeostasis, as well as changes that occur in the histological organization during the experiment, depending on the time elapsed since the induction of aseptic femoral head necrosis in Wistar rats. The results obtained demonstrate a developmental heterogeneity of osteodestruction in Wistar rats with a surgically created focus of femoral head hypoperfusion against the background of increased intra-articular pressure. In the first 2 weeks of the development of aseptic necrosis, there was a maximum expression of the hif-1a gene, which can be considered as a trigger of further disruption of bone metabolism. At the same time, mRNA expression of osteogenesis and osteoresorption genes was reduced. Most active osteolytic processes, detected by electron microscopy, as well as increased expression of osteoclastogenesis induction genes, were observed at week 6 of the experiment. An osteoreparative tendency in bone metabolism gradually increased since the onset of the experiment, and 2 months after the induction of femoral head avascular necrosis, there were revealed active osteoblasts and enhanced expression of bone matrix and osteoblastogenesis genes. Thus, the development of osteodestruction is an extremely heterogeneous process whose molecular patterns determining the activity of bone metabolism signaling pathways change dynamically in a time-dependent manner.

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Funding

The study was funded by the Grant of the President of the Russian Federation for Young Doctors and Candidates of Sciences (MK-4132.2022.3).

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Authors and Affiliations

  1. Kemerovo State Medical University of the Ministry of Health of the Russian Federation, Kemerovo, Russia

    N. A. Shabaldin & A. V. Shabaldin

  2. Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia

    A. V. Sinitskaya, A. V. Shabaldin & R. A. Mukhamadiyarov

Authors
  1. N. A. Shabaldin
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  2. A. V. Sinitskaya
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  3. A. V. Shabaldin
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  4. R. A. Mukhamadiyarov
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Contributions

Conceptualization, surgical manipulations, writing the manuscript (N.A.Sh.); data processing, editing the manuscript (A.V.Sh.); gene isolation and expression analysis (A.V.S.); electron microscopic examination, data analysis (R.A.M.).

Corresponding author

Correspondence to N. A. Shabaldin.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

The experiment was carried out in compliance with The Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes adopted by the Council of Europe (Strasbourg, France, 1986) and the Council Directive 86/609/EEC of November 24, 1986. The experimental protocol was approved by the Ethics Committee at the Kemerovo State Medical University of the Ministry of Health of the Russian Federation.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

Additional information

Translated by A. Polyanovsky

Russian Text © The Author(s), 2023, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2023, Vol. 109, No. 1, pp. 94–108https://doi.org/10.31857/S0869813923010107.

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Shabaldin, N.A., Sinitskaya, A.V., Shabaldin, A.V. et al. Expression Dynamics of Bone Homeostasis Genes in the Development of Aseptic Femoral Head Necrosis in Rats. J Evol Biochem Phys 59, 180–191 (2023). https://doi.org/10.1134/S0022093023010155

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