Results were analyzed using unpaired T-test with Welch’s correction. Results are presented as median and percentiles (25th and 75th).

Results were analyzed using unpaired T-test with Welch’s correction and are presented as median and percentiles (25th and 75th).

Results were analyzed using unpaired T-test with Welch’s correction and are presented as median and percentiles (25th and 75th).

Gene expression analysis in trabecular bone samples. (A) SOST mRNA levels resulted higher in T2D subjects versus Nondiabetic subjects (p<0.0001). (B) DKK-1 mRNA expression level was not different between groups (p=0.2022). (C) LEF-1 mRNA levels resulted lower in T2D subjects versus nondiabetics subjects (p=0.0136). (D) WNT10B mRNA expression level was lower in T2D subjects versus nondiabetic subjects (p=0.0302). (E) WNT5A mRNA resulted higher in T2D subjects versus nondiabetics subjects (p=0.0232). (F) COL1A1 mRNA levels resulted lower in T2D subjects versus Nondiabetic subjects (p=0.0482). (G) GSK3B mRNA levels resulted higher in T2D subjects versus Nondiabetic subjects (p=0.0456). (H-J) AXIN2, BETA-CATENIN, SFRP5 mRNA levels were not different between groups (p=0.2296, p=0.3073; p=0.1390). Data are expressed as fold changes over beta-actinMedians and interquartile ranges, differences between non-diabetics and T2D subjects were analyzed using Mann-Whitney test.

Relationship between AGEs (µg quinine/g collagen) bone content and mRNA level of the Wnt signaling key genes in T2D and non-diabetic subjects. (A) LEF-1 negatively correlated with AGEs (r=-0.7500; p=0.0255). (B) COL1A1 negatively correlated with AGEs (r=-0.9762; p=0.0004). (C) SOST mRNA level expression positively correlated with AGEs (r=0.9231; p<0.0001). (D) WNT5A mRNA expression level positively correlated with AGEs (r=0.6751; p=0.0322). (E) WNT10B mRNA expression level was not correlated with AGEs (r=-0.4883; p=0.1938). (F) DKK1 mRNA expression level was not correlated with AGEs (r=0.0476; p=0.9349). (G) GSK3B mRNA expression level was positively correlated with AGEs (r=0.7500; p=0.0255). (H) SFRP5 mRNA expression level was positively correlated with AGEs (r=0.7167; p=0.0369). (I) AXIN2 and (J) SFRP5 mRNA expression levels were not correlated with AGEs (r=0.5500, p=0.1328; r=0.2167, p=0.5809). Data were analyzed using nonparametric Spearman correlation analysis and r represents the correlation coefficient.

Relationship between fasting glucose levels (mg/dl) and disease duration with SOST and WNT5A mRNA levels. (A) SOST positively correlated with fasting glucose levels (r=0.4846; p=0.0043). (B) SOST positively correlated with disease duration (r=0.7107; p=0.0174). (C) WNT5A positively correlated with fasting glucose levels (r=0.5589; p=0.0037). (D) GSK3B positively correlated with fasting glucose levels (r=0.4901; p=0.0051). Data were analyzed using nonparametric Spearman correlation analysis and r represents the correlation coefficient.

Relationship between Young Modulus (MPa), Ultimate strength (MPa) and Yield strength (MPa) with mRNA levels of the Wnt signaling key genes in T2D and non-diabetic subjects. (A) SOST negatively correlated with Young Modulus (MPa); (r=-0.5675; p=0.0011). (B) LEF-1 positively correlated with Young Modulus (MPa); (r=0.4116; p=0.0295). (C) WNT10B positively correlated with Young Modulus (MPa); (r=0.6697; p=0.0001). (D) AXIN2 negatively correlated with Young Modulus (MPa); (r=-0.5523; p=0.0042). (E) BETA-CATENIN negatively correlated with Young Modulus (MPa); (r=-0.5244; p=0.0050). (F) SFRP5 negatively correlated with Young Modulus (MPa); (r=-0.4442; p=0.0437). (G) WNT10B positively correlated with Ultimate strength (MPa); (r=0.5392; p=0.0054). (H) AXIN2 negatively correlated with Ultimate strength (MPa); (r=-0.4180; p=0.0472). (I) BETA-CATENIN negatively correlated with Ultimate strength (MPa); (r=-0.5528; p=0.0034). (J) LEF-1 positively correlated with Yield strength (MPa); (r=0.4338; p=0.0495). (K) WNT10B positively correlated with Yield strength (MPa); (r=0.6632; p=0.0020). (L) GSK3B negatively correlated with Yield strength (MPa); (r=-0.4674; p=0.0245). (M) AXIN2 negatively correlated with Yield strength (MPa); (r=-0.5067; p=0.0319). (N) BETA-CATENIN negatively correlated with Yield strength (MPa); (r=-0.5491; p=0.0149). (O) SFRP5 negatively correlated with Yield strength (MPa); (r=-0.5357; p=0.0422). Data were analyzed using nonparametric Spearman correlation analysis and r represents the correlation coefficient.

Relationship between fasting glucose levels (mg/dl) and LEF-1, WNT5A, WNT10B, DKK-1, COL1A1 mRNA levels. (A-E) Data showed negative correlations between fasting glucose levels (mg/dl) and (A) LEF-1 (r=-0.3649; p=0.0613), (B) WNT10B (r=-0.0041; p=0.9863), (C) COL1A1 (r=-0.1157; p=0.5354), (D) DKK-1 (r=-0.0947; p=0.6522) mRNA levels. Data showed positive correlations between fasting glucose levels (mg/dl) with (E) AXIN2 (r=0.0993; p=0.6442), (F) BETA-CATENIN (r=0.2371; p=0.1991) and (G) SFRP5 (r=0.3767; p=0.0696). Data were analyzed using nonparametric Spearman correlation analysis and r represents the correlation coefficient.

Relationship between Young Modulus (MPa), Ultimate strength (MPa) and Yield strength (MPa) with mRNA levels of the Wnt signaling genes in T2D and non-diabetic subjects. (A) DKK-1 positively correlated with Young Modulus (MPa); (r=0.02857; p=0.9022). (B) COL1A1 positively correlated with Young Modulus (MPa); (r=0.2991; p=0.1397). (C) GSK3B negatively correlated with Young Modulus (MPa); (r=-0.3127; p=0.0814). (D) SOST negatively correlated with Ultimate strength (MPa); (r=-0.1468; p=0.4001). (E) DKK-1 negatively correlated with Ultimate strength (MPa); (r=0.1353; p=0.5694). (F) LEF-1 positively correlated with Ultimate strength (MPa); (r=0.2790; p=0.1588). (G) WNT5A negatively correlated with Ultimate strength (MPa); (r=-0.0143; p=0.9469). (H) COL1A1 positively correlated with Ultimate strength (MPa); (r=0.2138; p=0.3047). (I) GSK3B negatively correlated with Ultimate strength (MPa); (r=-0.3482; p=0.0594). (J) SFPR5 negatively correlated with Ultimate strength (MPa); (r=-0.3789; p=0.0994). (K) SOST positively correlated with Yield strength (MPa); (r=0.1009; p=0.6390). (L) DKK-1 positively correlated with Yield strength (MPa); (r=0.2786; p=0.3139). (M) WNT10B negatively correlated with Yield strength (MPa); (r=-0.0079; p=0.9744). (N) COL1A1 positively correlated with Yield strength (MPa); (r=0.2196; p=0.3260). (O) BETA-CATENIN negatively correlated with Young Modulus strength (MPa); (r=-0.1667; p=0.4953). (P) BETA-CATENIN negatively correlated with Ultimate strength (MPa); (r=-0.2797; p=0.2610). (Q) BETA-CATENIN negatively correlated with Yield strength (MPa); (r=-0.1813; p=0.5537). Data were analyzed using nonparametric Spearman correlation analysis and r represents the correlation coefficient.