INVESTIGADORES
PELLEGRINI Gretel Gisela
congresos y reuniones científicas
Título:
PTHrP-derived peptides restore bone mass and strength in diabetic mice: additive effect of mechanical loading
Autor/es:
MAYCAS M; MCANDREWS K; SATO AY; PELLEGRINI GG; BROWN DM; ALLEN MR; PLOTKIN L; ESBIRT P; GORTAZAR AR; BELLIDO T
Reunión:
Congreso; American Society for Bone and Mineral Research; 2015
Resumen:
There is an unmet need to treat bone fragilityin patients with diabetes mellitus. We examined herein the effectiveness of N-and C-terminal fragments of parathyroid hormone related peptide (PTHrP), incombination with mechanical loading, in counteracting skeletal deterioration ina mouse model of type 1 diabetes. Diabetes was induced in 4-month-old maleC57BL/6 mice by 5 consecutive daily ip injections of streptozotocin (45 mg/kg).Four weeks after injections, glucose levels were significantly higher in streptozotocin-injectedmice compared to non-diabetic control mice receiving saline (382±105 vs 179±27 mg/ml). At this time, diabetic mice were separatedin 3 groups and received 3 consecutive daily sc injections of PTHrP(1-37) (50 ìg/kg),PTHrP(107-111) (7 ìg/kg), or vehicle,followed by loading of the right ulnae for 1 min at 120 cycles/day at 3different magnitudes ranging from 1,995 to 2,500 µstrain. All mice were sacrificed12 days thereafter. Diabetic mice receiving vehicle exhibited a significant lower femoral BMDcompared to non-diabetic controls (decreased by 14±9%). In contrast, diabetic mice treated witheither PTHrP(1-37)or PTHrP(107-111) showed a gain of 3±4%and 3±5%, respectively, in femoral BMD,[LIP1]  similar[TM2]  to non-diabetic controls.Moreover, the decrease in trabecular thickness in the distal femur and incortical thickness at the mid-diaphysis exhibited by diabetic mice wasreversed by both PTHrP peptides. Furthermore, diabetic mice exhibited significantlylower mechanical (ultimate force and stiffness) and material (ultimate stressand toughness) properties quantified by femoral 3-point-bending, which wasrestored to non-diabetic control levels by both PTHrP peptides. In addition,CTX, a bone resorption marker, was increased in diabetic mice and reversed tonon-diabetic control levels by both PTHrP peptides. Higher magnitude loading wasneeded in diabetic mice to increase periosteal MAR and BFR/BS compared to non-diabeticcontrols. In addition, loading increased MAR and BFR/BS to higher levels indiabetic mice treated with either PTHrP peptide compared to diabetic micereceiving vehicle. In conclusion, these PTHrP peptides partially restored bone lossand strength and reversed increased resorption induced by diabetes, and workedadditively with mechanical loading to enhance periosteal bone formation in theappendicular skeleton of diabetic mice. Thus, this short treatment with both PTHrPpeptides reversed skeletal deterioration in diabetes [LIP1]I am not sure this is correct. Mice either gainor lose bone in % or exhibit a BMD value in mg/cm2. Or did you calculate the %BMD compare to the control (considering this one 100%)? [TM2]Thefirst % (comparingdiabeticmice vs non diabetic) itwascalculated % BMDcompare to control (consideringthisone 100%).Butthen, whenweare talkingabouttheincreased in thediabetic+PTHrPpeptidesmice, itisthe %delta(t final ? t at thebegining of thePTHrP treatments)