Diabetes mellitus comprehends a group of chronic metabolic disorders, associated with damage and dysfunction of distinct tissues, including bone. At the cellular level, an impaired osteoblastogenesis has been reported, affecting the viability, proliferation and functionality of osteoblasts and precursor populations, hampering the bone metabolic activity, remodeling and healing. Tetracyclines embrace a group of broad-spectrum antibacterial compounds with potential anabolic effects on the bone tissue, through antibacterial-independent mechanisms. Accordingly, this study aims to address the modulatory capability and associated molecular signaling of a low dosage doxycycline – a semi-synthetic tetracycline, in the functional activity of osteoblastic progenitor cells (bone marrow-derived mesenchymal stromal cells), established from a translational diabetic experimental model.

Bone marrow-derived mesenchymal stromal cells were isolated from streptozotocin-induced diabetic Wistar rat with proven osteopenia. Cultures were characterized, in the presence of doxycycline (1 μg ml⁻¹) for proliferation, metabolic activity, apoptosis, collagen synthesis and relevant gene expression with the osteogenic and adipogenic program. The activation of the Wnt/β-catenin pathway was further detailed.

Doxycycline normalized the viability, proliferation and metabolic activity of the established cultures, further decreasing cell apoptosis, to levels similar to control. The addition of this drug to the culture environment further increased the osteogenic activation, upregulating the expression of osteogenic markers and collagen synthesis, at the same time that a decreased adipogenic priming was attained. These processes were found to me mediated, at least in part, by the restoration of the signaling through the Wnt/β-catenin pathway.

糖尿病包括一组慢性代谢疾病，与包括骨骼在内的不同组织的损伤和功能障碍有关。在细胞水平上，已经报道了成骨细胞发生受损，影响成骨细胞和前体细胞的活力，增殖和功能，阻碍了骨代谢活性，重塑和愈合。四环素包含一组广谱抗菌化合物，它们通过不依赖抗菌的机制对骨骼组织具有潜在的合成代谢作用。因此，本研究旨在探讨低剂量强力霉素（一种半合成四环素）在成骨祖细胞（骨髓源性间充质基质细胞）的功能活性中的调控能力和相关的分子信号传导，

从链脲佐菌素诱导的糖尿病性Wistar大鼠中分离出骨髓来源的间充质基质细胞，并证实其骨质减少。在强力霉素（1μgml ^-1）存在下，通过成骨和成脂程序对培养物进行增殖，代谢活性，凋亡，胶原蛋白合成和相关基因表达的表征。Wnt /β-catenin途径的激活进一步详述。

强力霉素使已建立培养物的活力，增殖和代谢活性正常化，进一步降低了细胞凋亡，达到了与对照相似的水平。在培养环境中添加该药物可进一步增强成骨激活，上调成骨标记物的表达和胶原蛋白的合成，同时降低成脂引发作用。我发现这些过程至少部分是通过Wnt /β-catenin途径的信号转导介导的。