• Animals
• Neurofibromatosis 1/diet therapy
• Neurofibromatosis 1/pathology
• Neurofibromatosis 1/metabolism
• Neurofibromatosis 1/genetics
• Mice
• Disease Models, Animal
• Mice, Knockout
• Phenotype
• Neurofibromin 1/genetics
• Neurofibromin 1/metabolism
• Porosity
• Bone and Bones/metabolism
• Bone and Bones/pathology
• Lipid Metabolism
• X-Ray Microtomography
• Male
• Bone Density
• Diet

• Children’s Tumor Foundation Drug Discovery Initiative (DDI program)
• Luminesce Alliance (luminesce.org.au)
• Research Training Program (RTP) Scholarships from the Australian Government

• Bone
• Lacuno-canalicular network
• Osteocyte
• Resin cast etching
• Scanning electron microscopy

Osteoporosis is a systemic bone disease characterized by decreased bone mass, impaired bone mass, and reduced bone strength that leads to increased bone fragility and fracture. Type 2 diabetes mellitus (T2DM) complicated with osteoporosis is a common systemic metabolic bone disease, and reduced bone mass and bone strength are considered the main clinical features; however, the pathogenesis of this disease has not been fully clarified. Its occurrence is considered related to sex, age, and genetic factors. There are many risk factors for diabetes complicated with osteoporosis. Therefore, exploring these risk factors will help prevent it.

To investigate the relationships among serum glucagon-like peptide-1 (GLP-1) levels, matrix Gla protein (MGP) levels, and diabetes with osteoporosis.

Sixty patients with T2DM complicated with osteoporosis confirmed by the endocrinology department of our hospital were selected as the case group. Sixty T2DM patients with bone loss were selected as the control group. Sixty healthy participants were selected as the healthy group. The general data, bone mineral density index, and bone metabolic markers of the three groups were compared. The relationships among GLP-1 levels, MGP levels, and the bone mineral density index of the case group were analyzed using linear correlation analysis and a logistic regression model.

Differences in sex, smoking, and drinking among the case group, control group, and healthy group were not statistically significant (P > 0.05). The mean age of the case group was older than those of the control and healthy groups (P < 0.05). The body mass index, fasting plasma glucose level, HbA1c level, hypertension rate, and coronary heart disease rate of the case and control groups were higher than those of the healthy group (P < 0.05). The serum GLP-1 and MGP levels of the case group were lower than those of the control and healthy groups; these differences were statistically significant (P < 0.05). The serum GLP-1 and MGP levels of the control group were lower than those of the healthy group; these differences were statistically significant (P < 0.05). The serum GLP-1 and MGP levels of the case group were significantly positively correlated with the bone mineral density values of the hip and lumbar spine (P < 0.05). The results of the logistic regression model showed that age and duration of diabetes were independent risk factors for osteoporosis in diabetic patients (P < 0.05) and that increased GLP-1 and MGP values were protective factors against osteoporosis in diabetic patients (P < 0.05).

Serum GLP-1 and MGP levels of diabetic patients with osteoporosis were significantly decreased and positively correlated with bone mineral density and were independent risk factors for osteoporosis in diabetic patients.

• Glucagon-like peptide-1
• Matrix Gla protein
• Diabetes mellitus
• Osteoporosis
• Bone mineral density
• Systemic bone disease

Neurofibromatosis 1 (NF1) presents a wide range of clinical manifestations, including bone alterations. Studies that seek to understand cellular and molecular mechanisms underlying NF1 orthopedic problems are of great importance to better understand the pathogenesis and the development of new therapies. Dental pulp stem cells (DPSCs) are being used as an in vitro model for several diseases and appear as a suitable model for NF1. The aim of this study was to evaluate in vitro chondrogenic differentiation of DPSCs from individuals with NF1 using two-dimensional (2D) and three-dimensional (3D) cultures.

To fulfill the criteria of the International Society for Cellular Therapy, DPSCs were characterized by surface antigen expression and by their multipotentiality, being induced to differentiate towards adipogenic, osteogenic, and chondrogenic lineages in 2D cultures. Both DPSCs from individuals with NF1 (NF1 DPSCs) and control cultures were positive for CD90, CD105, CD146 and negative for CD13, CD14, CD45 and CD271, and successfully differentiated after the protocols. Chondrogenic differentiation was evaluated in 2D and in 3D (pellet) cultures, which were further evaluated by optical microscopy and transmission electron microscopy (TEM). 2D cultures showed greater extracellular matrix deposition in NF1 DPSCs comparing with controls during chondrogenic differentiation. In semithin sections, control pellets hadhomogenous-sized intra and extracelullar matrix vesicles, whereas NF1 cultures had matrix vesicles of different sizes. TEM analysis showed higher amount of collagen fibers in NF1 cultures compared with control cultures.

NF1 DPSCs presented increased extracellular matrix deposition during chondrogenic differentiation, which could be related to skeletal changes in individuals with NF1.

The online version of this article (10.1186/s13023-018-0843-1) contains supplementary material, which is available to authorized users.

• Cell culture
• Cell differentiation
• Chondrogenesis
• Neurofibromatosis 1

Gfi1 is a key molecule in hematopoietic lineage development and mutations in GFI1 cause severe congenital neutropenia (SCN). Neutropenia is associated with low bone mass, but the underlying mechanisms are poorly characterized. Using Gfi1 knock-out mice (Gfi1-ko/ko) as SCN model, we studied the relationship between neutropenia and bone mass upon different pathogen load conditions. Our analysis reveals that Gfi1-ko/ko mice kept under strict specific pathogen free (SPF) conditions demonstrate normal bone mass and survival. However, Gfi1-ko/ko mice with early (nonSPF) or late (SPF+nonSPF) pathogen exposure develop low bone mass. Gfi1-ko/ko mice demonstrate a striking rise of systemic inflammatory markers according to elevated pathogen exposure and reduced bone mass. Elevated inflammatory cytokines include for instance Il-1b, Il-6, and Tnf-alpha that regulate osteoclast development. We conclude that low bone mass, due to low neutrophil counts, is caused by the degree of systemic inflammation promoting osteoclastogenesis.