Biology subjects

Hrovat, K.

Publications and source records attributed to Hrovat, K..

3 recordsLinked to original sources

bioRxiv2026

Suppressing Bone Resorption and Promoting Mineralization with Tetracycline Derivatives

Osteoporosis is a progressive skeletal disorder characterized by decreased bone mass and an increased risk of fracture. Current treatments are limited by adverse effects and poor long-term compliance, necessitating alternative therapeutic approaches. Tetracycline (TC) derivatives, which are traditionally used as antibiotics, have shown promise in modulating bone remodeling. In this study, the effects of TC and three TC derivatives--oxytetracycline (OC), doxycycline (DC), and minocycline (MC)--on osteoclast and osteoblast activities were investigated using in vitro human cell models and in vivo zebrafish assays. All TC derivatives inhibited osteoclast differentiation and bone resorption, as shown by reductions in the number of TRAP-positive cells, resorption pit volume, and matrix metalloproteinase (MMP)-2/MMP-9 secretion. DC demonstrated the most potent inhibitory effects across all concentrations. Low to moderate concentrations of OC, DC, and MC promoted osteoblast proliferation and mineralization, whereas high doses inhibited these processes. Confocal imaging confirmed the accumulation of TC derivatives in mineralized bone nodules. Zebrafish studies revealed dose-dependent suppression of craniofacial bone development at higher concentrations. These findings highlight the dose dependent, dual effects of TC derivatives on bone cells (osteoblasts and osteoclasts) and underscore the potential of these agents as dual-function therapies for osteoporosis.

pharmacology and toxicology↗

bioRxiv2026

Electrical Surface Polarization as a Functionalization Strategy to Improve Bone Regeneration of Apatite-Based Graft Materials

Apatite-based bone graft materials are widely used for bone regeneration; however, their limited bioactivity and slow remodeling often hinder complete replacement by newly formed bone. Electrical surface polarization has emerged as a promising non-chemical strategy to modify biomaterial surface properties without altering bulk characteristics. In this study, we investigated the effects of electrical surface polarization on apatite-based biomaterials using synthesized carbonate apatite (CA) for mechanistic in vitro evaluation and a clinically relevant xenograft material for in vivo validation. Material characterization confirmed the formation of B-type carbonate apatite with bone-like mineral composition. Thermally stimulated depolarization current measurements verified successful induction of surface charges, with polarization intensity dependent on treatment conditions. In vitro studies using human peripheral blood-derived osteoclast precursors demonstrated that electrically polarized CA surfaces significantly enhanced osteoclast differentiation and resorptive activity compared to non-polarized controls, with the strongest effects observed on positively polarized surfaces. Three-dimensional analysis revealed increased resorption pit depth and volume, indicating enhanced osteoclast functionality. In vivo implantation of polarized xenograft materials into rat femoral defects resulted in significantly increased new bone formation and improved implant-bone integration compared to non-polarized materials. Higher polarization conditions promoted more mature bone tissue formation and greater bone-material affinity. These results demonstrate that electrical surface polarization effectively modulates osteoclast-material interactions and enhances bone regeneration, highlighting its potential as a simple and translatable functionalization strategy for apatite-based bone graft materials.

bioengineering↗

bioRxiv2024

Bone mechano-response is driven by locomotion transitions during vertebrate evolution

The skeleton supports the muscles in keeping the body upright against gravity while enduring thousands of daily loads. In this study, we investigated non-collagenous bone matrix proteins using osteoblast cell cultures and phylogenetic analyses to identify the molecular mechanisms involved in mechanical loading. The results indicate that the bone mechano-response is an evolutionary-driven process and that several non-collagenous proteins may significantly regulate the bones response to mechanical stress. According to our results, two significant evolutionary transitions in vertebrate locomotion shaped the roles of non-collagenous proteins in humans: the water-to-land transition, which increased mechanical stress on the limbs, and the evolution to bipedalism in humans, which altered the distribution of stress on the lower and upper limbs. Fetuin A, positively selected in both evolutionary transitions, showed the most significant expression change during mechanical stimulation.

evolutionary biology↗