Biology subjects

Shimochi, S.

Publications and source records attributed to Shimochi, S..

3 recordsLinked to original sources

bioRxiv2026

Towards Understanding the Microenvironmental Control of Reindeer Antler Regeneration

Deer antlers are the only mammalian appendages capable of complete periodic regeneration and therefore provide a natural model for investigating mechanisms of skeletal regeneration. However, current knowledge of the structural and molecular characteristics of the regenerative antler microenvironment remains incomplete. Here, we compared antler tip and antler base tissues from Rangifer tarandus (reindeer) with mature metacarpal cortical bone using structural, compositional, histological, and proteomic analyses. Antler tissues exhibited smaller and less crystalline apatite structures, elevated carbonate substitution, and higher organic matrix content compared with metacarpal bone, indicating an immature mineral phase. Antlers also exhibited lower bone mineral density, greater porosity, reduced bone volume fraction, and greater trabecular separation, particularly in central regions, consistent with a dynamic remodeling microenvironment. Histological examination revealed abundant active osteons and extensive osteoid seams in antler tissues, whereas metacarpal bone predominantly comprised mature lamellar bone with limited remodeling activity. Proteomic profiling identified distinct extracellular matrix signatures between antler and metacarpal tissues. Metacarpal bone was enriched in proteins associated with skeletal homeostasis, mechanotransduction, and bone remodeling, whereas antler tissues were enriched in proteins involved in extracellular matrix reorganization, metabolic adaptation, and regeneration. Collectively, these findings indicate that reindeer antlers possess a specialized regenerative skeletal microenvironment characterized by immature mineral organization, active remodeling, and distinct molecular signatures associated with rapid tissue growth. These results provide new insights into the biological basis of mammalian appendage regeneration and may facilitate the development of regenerative strategies for bone repair and skeletal tissue engineering.

developmental biology↗

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↗

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↗