Adverse changes in cortical and trabecular bone compartments of the femur in rats with adjuvant-induced arthritis after one remodelling cycle

It is widely known that rheumatoid arthritis (RA) is associated with articular bone damage. However, there is still not enough information on whether the inflammatory process can deteriorate bone microstructure outside the joint as well. Furthermore, the impact of RA on the microscopic structure of cortical and trabecular bone, including parameters of bone microarchitecture, strength, and geometry after one remodelling cycle, has not been determined, yet. Therefore, this study investigated possible alterations in both cortical and trabecular bone compartments of the femur in a rat model of adjuvant-induced arthritis (AA) 28 days post disease induction. AA was generally evoked by a single intradermal injection ofsuspension of heat-inactivated Mycobacterium butyricumin incomplete Freund’s adjuvant. We have found that AA resulted in inflammation as evidenced by increased hind paw swelling, decreased levels of circulating albumin, and elevated levels of nitrite/nitrate, interleukin-1β. Detrimental changes in examined bone parameters related to microarchitecture, strength, and geometry were revealed in AA rats. Overall, AA was associated with bone loss, decreased bone mineral density in bothcortical and trabecular bone compartments, as well as reduced mechanical competence, and more intense vascularization in the cortical bone. According to our results, AA-related inflammation caused structural degradation of cortical and trabecular bone quality, as well as mechanical weakness in the femoral diaphysis leading to bone fragility after only one remodelling cycle. The findings focused on the femoral diaphysis, which is located outside the joint, are the first in this field of research

The Effects of Prolonged Treatment with Cemtirestat on Bone Parameters Reflecting Bone Quality in Non-Diabetic and Streptozotocin-Induced Diabetic Rats

Cemtirestat, a bifunctional drug acting as an aldose reductase inhibitor with antioxidant ability, is considered a promising candidate for the treatment of diabetic neuropathy. Our study firstly examined the effects of prolonged cemtirestat treatment on bone parameters reflecting bone quality in non-diabetic rats and rats with streptozotocin (STZ)-induced diabetes. Experimental animals were assigned to four groups: non-diabetic rats, non-diabetic rats treated with cemtirestat, diabetic rats, and diabetic rats treated with cemtirestat. Higher levels of plasma glucose, triglycerides, cholesterol, glycated hemoglobin, magnesium, reduced femoral weight and length, bone mineral density and content, parameters characterizing trabecular bone mass and microarchitecture, cortical microarchitecture and geometry, and bone mechanical properties were determined in STZ-induced diabetic versus non-diabetic rats. Treatment with cemtirestat did not affect all aforementioned parameters in non-diabetic animals, suggesting that this drug is safe. In diabetic rats, cemtirestat supplementation reduced plasma triglyceride levels, increased the Haversian canal area and slightly, but insignificantly, improved bone mineral content. Nevertheless, the insufficient effect of cemtirestat treatment on diabetic bone disease does not support its use in the therapy of this complication of type 1 diabetes mellitus

Impact of ergothioneine, hercynine, and histidine on oxidative degradation of hyaluronan and wound Healing

A high-molecular weight hyaluronan is oxidatively degraded by Cu(II) ions and ascorbate—the so called Weissberger biogenic oxidative system—which is one of the most potent generators of reactive oxygen species, namely •OH radicals. Ergothioneine, hercynine, or histidine were loaded into chitosan/hyaluronan composite membranes to examine their effect on skin wound healing in ischemic rabbits. We also explored the ability of ergothioneine, hercynine, or histidine to inhibit hyaluronan degradation. Rotational viscometry showed that ergothioneine decreased the degree of hyaluronan radical degradation in a dose-dependent manner. While histidine was shown to be potent in scavenging •OH radicals, however, hercynine was ineffective. In vivo results showed that the addition of each investigated agent to chitosan/hyaluronan membranes contributed to a more potent treatment of ischemic skin wounds in rabbits compared to untreated animals and animals treated only with chitosan/hyaluronan membranes