The impact of the diabetic micro-environment on bone and its healing process

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease which has become a socio-economical burden worldwide. Recently, increasing evidence shows that T2DM negatively affects the skeletal system, in terms of increased fracture risk, compromised bone material and impaired bone healing. However, despite the efforts made in the field, the mechanisms governing this pathology remain unclear. The doctoral project aimed at exploring the key microstructural, biomechanical and biological micro-environmental characteristics of bone tissue and its healing under T2DM conditions via an interdisciplinary approach, crossing the boundaries between the fields of bone biology, endocrinology, biomedical micro-Imaging, and biomechanics. To accomplish this, high resolution microfocus computed tomography (microCT), 3-point bending mechanical test, finite element modeling, Raman microspectroscopy and in vitro characterization of osteocondroprogenitor cells were implemented on a diet-induced obese mouse model. Bone microarchitectural and material properties were found compromised by the diabetic micro-environment (deterioration of cortical/trabecular compartments and accumulation of advanced glycation end-products, respectively), thus inducing the biomechanical dysfunctionality observed in the bones of these animals. Furthermore, contrast-enhanced microCT revealed for the first time the simultanous 3D visualization and quantification of the skeletal tissues involved in the fracture healing process. The accumulation of both mineralized and unmineralized cartilage, and the increased presence of adiposity in the fractured callus of the diabetic bone demonstrated that fracture healing is impaired in these animals, compared to age-matched lean controls. Moreover, the characterization of periosteum-derived cells cultured in vitro under hyperglycemic conditions revealed that high concentrations of glucose compromised their proliferation and trilineage differentiation processes, suggesting that the altered nature of these osteochondroprogenitors may be contributing to the impaired diabetic bone fracture healing process seen in vivo. Overall, the outcomes of this doctoral project further unraveled the pathological effects of T2DM on bone tissue properties and its healing process.

Jaar van publicatie:2019