Synthetic Peptide CK2.3 Enhances Bone Mineral Density in Senile Mice
Open Access
- 1 January 2018
- journal article
- Published by OMICS Publishing Group in Journal of Bone Research
Abstract
Osteoporosis is a silent disease caused by low bone mineral density that results in bone fractures in 1 out of 2 women and 1 in 4 men over the age of 50. Although several treatments for osteopenia and osteoporosis are available, they have severe side effects and new treatments are desperately needed. Current treatments usually target osteoclasts and inhibit their activity or differentiation. Treatments that decrease osteoclast differentiation and activity but enhance osteogenesis and osteoblast activity are not available. We recently developed a peptide, CK2.3, that induces bone formation and increases bone mineral density as demonstrated by injection over the calvaria of 6 to 9-day-old mice and tail vein injection of 8-week-old mice. CK2.3 also decreased osteoclast formation and activity. However, these studies raise questions: does CK2.3 induce similar results in old mice and if so, what is the effective CK2.3 concentration and, is the bone mineral density of vertebrae of the spinal column increased as well? CK2.3 was systematically injected into the tail vein of female 6-month old mice with various concentrations of CK2.3: 0.76 μg/kg, 2.3 μg/kg, or 6.9 μg/kg per mice. Mice were sacrificed one week, two weeks, and four weeks after the first injection. Their spines and femurs were collected and analyzed for bone formation. Femur and lumbar spine analyses found increased bone mineral density (BMD) and mineral apposition rate, with greater stiffness observed in femoral samples four weeks after the first injection. Histochemistry showed that osteoclastogenesis was suppressed in CK2.3 treated senile mice. For the first time, this study showed the increase of lumbar spine BMD by CK2.3. Moreover, it showed that enhancement of femur BMD was accompanied by increased femur stiffness only at medium concentration of CK2.3 four weeks after the first injection indicating the maintenance of bone’s structural integrity by CK2.3.Keywords
This publication has 33 references indexed in Scilit:
- Gender Disparities in OsteoporosisJournal of Clinical Medicine Research, 2017
- Hospitalizations for osteoporosis-related fractures: Economic costs and clinical outcomesBone Reports, 2016
- A concise review of testosterone and bone healthClinical Interventions in Aging, 2016
- Bovine parathyroid hormone enhances osteoclast bone resorption by modulating V-ATPase through PTH1RInternational Journal of Molecular Medicine, 2015
- Bone morphogenetic protein 2 signaling in osteoclasts is negatively regulated by the BMP antagonist, twisted gastrulationJournal of Cellular Biochemistry, 2010
- Bone morphogenic protein 2 directly enhances differentiation of murine osteoclast precursorsJournal of Cellular Biochemistry, 2009
- Bone remodelling: its local regulation and the emergence of bone fragilityBest Practice & Research Clinical Endocrinology & Metabolism, 2008
- Dynamics and interaction of caveolin-1 isoforms with BMP-receptorsJournal of Cell Science, 2005
- Bone Mineral Density in Diagnosis of OsteoporosisJournal of Clinical Densitometry, 2000
- Value of Single Photon Absorptiometry in Osteoporosis ScreeningClinical Nuclear Medicine, 1988