Bone Morphogenetic Protein-6 Attenuates Type 1 Diabetes Mellitus-Associated Bone Loss

Abstract

Patients with type 1 diabetes mellitus (T1DM) often suffer from osteopenia or osteoporosis. Although most agree that T1DM‐induced hyperglycemia is a risk factor for progressive bone loss, the mechanisms for the link between T1DM and bone loss still remain elusive. In this study, we found that bone marrow‐derived mesenchymal stem cells (BMSCs) isolated from T1DM donors were less inducible for osteogenesis than those from non‐T1DM donors and further identified a mechanism involving bone morphogenetic protein‐6 (BMP6) that was produced significantly less in BMSCs derived from T1DM donors than that in control cells. With addition of exogenous BMP6 in culture, osteogenesis of BMSCs from T1DM donors was restored whereas the treatment of BMP6 seemed not to affect non‐T1DM control cells. We also demonstrated that bone mineral density (BMD) was reduced in streptozotocin‐induced diabetic mice compared with that in control animals, and intraperitoneal injection of BMP6 mitigated bone loss and increased BMD in diabetic mice. Our results suggest that bone formation in T1DM patients is impaired by reduction of endogenous BMP6, and supplementation of BMP6 enhances osteogenesis of BMSCs to restore BMD in a mouse model of T1DM, which provides insight into the development of clinical treatments for T1DM‐assocaited bone loss. stem cells translational medicine 2019;8:522–534

Impairment of maturation of BMP-6 (35kDa) correlates with delayed fracture healing in experimental diabetes

“…Although the potential participation of BMP-6 in bone formation was indicated in previous researches [18,[24][25][26], the role of the compound in diabetes related impairment of fracture healing has not been elucidated. The novel finding of this study indicates a particular member of the BMP-6 family, with a molecular weight of 35 kDa, may play a role in fracture healing.…”

Bone Marrow Mesenchymal Stromal Cells (BMMSCs) Augment Osteointegration of Dental Implants in Type 1 Diabetic Rabbits: An X-Ray Micro-Computed Tomographic Evaluation

“…It is well known that diabetes-induced hyperglycemia can diminish the osteoinductive ability of BMMSCs [45]. Increased levels of tissue necrotic factor (TNF) and reduction in bone morphogenetic protein-6 (BMP-6) are some of the reported mechanisms that could be implicated for delayed or failed osseointegration in diabetic cases [45,46]. Coating of polylactic-co-glycolic acid (PGLA) containing miR204 inhibitors and gold nanoparticles on the implant to overcome such attenuation has been reported to enhance implant homing [47].…”

Impairment of maturation of BMP-6 (35kDa) correlates with delayed fracture healing in experimental diabetes

“…Although the potential participation of BMP-6 in bone formation was indicated in previous researches [18,[24][25][26], the role of the compound in diabetes related impairment of fracture healing has not been elucidated. The novel finding of this study indicates a particular member of the BMP-6 family, with a molecular weight of 35 kDa, may play an important role in fracture healing.…”