Biology subjects

Makela, K.

Publications and source records attributed to Makela, K..

4 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↗

bioRxiv2021

Surface electric fields increase human osteoclast resorption through improved wettability on carbonate-incorporated apatite

Osteoclast-mediated bioresorption can be of an efficient means of incorporating the dissolution of biomaterials in the bone remodeling process. Because of compositionally and structurally close resemblance of biomaterials with the natural mineral phases of the bone matrix, synthetic carbonate-substituted hydroxyapatite (CA) is considered as an ideal clinical biomaterial. The present study therefore investigated the effects of electrical polarization on the surface characteristics and interactions with human osteoclasts of hydroxyapatite (HA) and CA. Electrical polarization was found to improve the surface wettability of these materials by increasing the surface free energy, and this effect was maintained for one month. Analyses of human osteoclast cultures established that CA subjected to a polarization treatment accelerated osteoclast resorption but did not affect the early differentiation phase or the adherent morphology of the osteoclasts as evaluated by staining. These data suggest that the surface characteristics of the CA promoted osteoclast resorption. The results of this work are expected to contribute to the design of cell-mediated biomaterials that can be resorbed by osteoclasts after fulfilling their primary function as a scaffold for bone regeneration.

bioengineering↗

bioRxiv2020

Prevalence of genetically similar Flavobacterium columnare phages across aquaculture environments reveals a strong potential for pathogen control

Intensive aquaculture conditions expose fish to bacterial infections, leading to significant financial losses, extensive antibiotic use and risk of antibiotic resistance in target bacteria. Flavobacterium columnare causes columnaris disease in aquaculture worldwide. To develop a bacteriophage-based control of columnaris disease, we isolated and characterized 126 F. columnare strains and 63 phages against F. columnare from Finland and Sweden. Bacterial isolates were virulent on rainbow trout (Oncorhynchus mykiss) and fell into four previously described genetic groups A, C, E and G, with genetic groups C and E being the most virulent. Phage host range studied against a collection of 228 bacterial isolates demonstrated modular infection patterns based on host genetic group. Phages infected contemporary and previously isolated bacterial hosts, but bacteria isolated most recently were generally resistant to previously isolated phages. Despite large differences in geographical origin, isolation year or host range of the phages, whole genome sequencing of 56 phages showed high level of genetic similarity to previously isolated F. columnare phages (Ficleduovirus, Myoviridae). Altogether, this phage collection demonstrates a potential to be used in phage therapy. Significance StatementBacteriophages were discovered already over a century ago, and used widely in treatment of bacterial diseases before the era of antibiotics. Due to harmful effects of antibiotic leakage into environment, aquaculture is a potential target for phage therapy. However, the development of efficient phage therapy approach requires detailed characterization of bacterial pathogen virulence and phage host range. Here, we describe phage-bacterium interactions in the fish pathogen Flavobacterium columnare. We found that genetically similar phages are found from different fish farms, and their infectivity cluster according to genetic group of bacteria. In addition, phages were able to infect bacterial hosts from other farms, which is a preferable trait considering phage therapy approach. However, the most recently isolated phages had broader host range than the previously isolated phages, suggesting a response in the phage community to evolution of resistance in the bacteria. These results show that designing phage therapy for aquaculture (and other) systems needs consideration of both temporal and geographical aspects of the phage-bacterium interaction.

microbiology↗