(P03-066-23) Conjugated Linoleic Acid (CLA) Attenuates the Negative Effects of Thiazolidinedione Medication on Bone Remodeling

Objectives: Diabetes mellitus (DM) is a metabolic disorder marked by hyperglycemia. Thiazolidinediones (TZDs) are an anti-diabetic medication with remarkable insulin-sensitizing potential, however, negatively affect the bone health of DM patients. Maintaining healthy bones relies on a delicate balance between bone-building cells called osteoblasts and bone-resorbing cells called osteoclasts. Conjugated linoleic acid (CLA), specifically the t10c12-CLA isomer, is a compound approved by the FDA that has been shown to promote bone formation and reduce bone resorption. This study aims to investigate whether co-treatment with CLA can lessen the negative effects of TZDs on bone remodeling. We hypothesize that CLA co-treatment attenuates TZD-mediated deterioration of bone remodeling.

Methods: The study examined the impact of CLA co-treatment on the differentiation and gene expression in 3 cell lineages. RAW264.7 cells were used to assess osteoclastogenesis, while mesenchymal stromal cells (MSCs) were used to evaluate adipogenesis and osteogenesis. The differentiation of these cells was analyzed using various techniques, including TRAP staining, F-actin ring/nuclear immunostaining, Oil-Red-O and LipidTOX staining, and alkaline-phosphatase staining and OsteoImageTM Mineralization Assay. Gene expression analysis was conducted through real-time RT-PCR.

Results: When cells were stimulated according to their specific lineage, co-treatment with CLA resulted in increased osteogenesis and higher levels of RUNX2, OPG, and IGF1-R. Conversely, CLA co-treatment led to decreased adipogenesis and lower levels of FAB4, ADIPSIN, and PPAR-g. Additionally, CLA co-treatment resulted in reduced osteoclastogenesis and lower levels of TRAP5b, CTSK, ITGb3, RANK, c-FOS, MMP-9, and MMP-13 compared to cells treated with TZDs alone.

Conclusions: Based on our results, it appears that co-treatment with CLA has the potential to counteract the negative effects of TZDs on bone health. This may occur through the induction of osteogenesis and a reduction in bone-marrow adipogenic and osteoclastogenic bone resorption. CLA could be a valuable addition to the treatment regimen of people with diabetes, improving their overall quality of life.

Funding Sources: Qatar University Grants: QUCG-CAS-21/22-2; QUST-1-CAS-2023-817; QUST-1-CAS-2022-401; QUST-1-CAS-2022-405