Effect of Mesenc
Effect of Mesenchymal Stem Cells Systemic Implantation on
Glucocorticoid- Induced Osteoporosis in Male Rats: A Comparative Study with
Alendronate
Hanan
Fathy Al-Saeed1 and Ahmed Hashem Amin2
1Department
of Physiology, Faculty of Medicine for Girls, Al-Azhar University, Egypt.
2Department
of Orthopedic, Faculty of Medicine, Zagazig University, Egypt.
Abstract: Objectives: The present study aims to assess if
mesenchymal stem cell (MSCs) transplantation could be useful in the treatment
of glucocorticoid-induced osteoporosis (GIO) in rats and to compare the
effectiveness of this therapy with a commonly prescribed bisphosphonate
(alendronate). Moreover, it aims to clarify the role of osteoprotegerin (OPG)
in the development of GIO. Methods: Forty adult male albino rats
were divided into four equal groups, ten rats each. The first group (group I)
served as healthy control group, while osteoporosis was induced in the rest of
the rats by daily intraperitoneal (ip) injection of 20 mg/kg dexamethasone for
3 wk after which the osteoporotic rats were divided into three groups: group
II: osteoporotic non treated group, group III: injected once with bone marrow
derived-mesenchymal stem cell (BMSCs) into tail vein and group IV was given ip
injections of alendronate (ALN) 60 mg/kg in saline every other day for 4 weeks.
On the 28th day of BMSCs implantation, blood samples were
obtained and sera were separated for estimation of bone turnover markers
(osteocalcin and hydroxyproline). Bone samples were collected. Osteoprotegerin
gene expression was determined with real time-polymerase chain reaction
(RT-PCR). Also, histopathological examination of bone was done.Results: In
the present study Glucocorticoids-induced osteoporosis is characterized by
significant decrease in serum levels of osteocalcin (OC) and OPG gene
expression in tibia with significant increase of hydroxyproline (HYP) levels in
urine. At the end of the treatment period, both BMSCs and ALN increased serum
levels of OC compared to GIO rats. There was no significant difference observed
between two treated groups. Both BMSCs and ALN significantly reduced HYP urine
levels compared to GIO rats. However, ALN, known as an antiresorptive
compound lowered hydroxyproline levels significantly more when compared with
BMSCs-treated group. Also, OPG gene expression was significantly higher in the
ALN-treated group, compared to GIO group, control group and BMSCs-treated
group. Also, BMSCs-treated group showed significant increase in OPG gene
expression compared to GIO group but its level still lower than the control
level. Conclusion: Bone regeneration through induction of BMSCs
could promote osteogenesis and provide a rational therapeutic strategy for
osteoporosis. However, new approach to increase the homing and retention of the
BMSCs to bone is required to augment bone formation and increase bone mass for
the treatment of osteoporosis.
[Hanan Fathy Al-Saeed and
Ahmed Hashem Amin. Effect of Mesenchymal Stem Cells Systemic
Implantation on Glucocorticoid- Induced Osteoporosis in Male Rats: A
Comparative Study with Alendronate. J
Am Sci 2012;8(10):641-650]. (ISSN: 1545-1003). http://www.jofamericanscience.org.
87
Keywords: glucocorticoid, osteoporosis, mesenchymal
stem cells, osteoprotegerin, bone turnover markers. Full Text 87
Hanan Fathy Al-Saeed1 and Ahmed Hashem Amin2
1Department of Physiology, Faculty of Medicine for Girls, Al-Azhar University, Egypt.
2Department of Orthopedic, Faculty of Medicine, Zagazig University, Egypt.
Abstract: Objectives: The present study aims to assess if mesenchymal stem cell (MSCs) transplantation could be useful in the treatment of glucocorticoid-induced osteoporosis (GIO) in rats and to compare the effectiveness of this therapy with a commonly prescribed bisphosphonate (alendronate). Moreover, it aims to clarify the role of osteoprotegerin (OPG) in the development of GIO. Methods: Forty adult male albino rats were divided into four equal groups, ten rats each. The first group (group I) served as healthy control group, while osteoporosis was induced in the rest of the rats by daily intraperitoneal (ip) injection of 20 mg/kg dexamethasone for 3 wk after which the osteoporotic rats were divided into three groups: group II: osteoporotic non treated group, group III: injected once with bone marrow derived-mesenchymal stem cell (BMSCs) into tail vein and group IV was given ip injections of alendronate (ALN) 60 mg/kg in saline every other day for 4 weeks. On the 28th day of BMSCs implantation, blood samples were obtained and sera were separated for estimation of bone turnover markers (osteocalcin and hydroxyproline). Bone samples were collected. Osteoprotegerin gene expression was determined with real time-polymerase chain reaction (RT-PCR). Also, histopathological examination of bone was done.Results: In the present study Glucocorticoids-induced osteoporosis is characterized by significant decrease in serum levels of osteocalcin (OC) and OPG gene expression in tibia with significant increase of hydroxyproline (HYP) levels in urine. At the end of the treatment period, both BMSCs and ALN increased serum levels of OC compared to GIO rats. There was no significant difference observed between two treated groups. Both BMSCs and ALN significantly reduced HYP urine levels compared to GIO rats. However, ALN, known as an antiresorptive compound lowered hydroxyproline levels significantly more when compared with BMSCs-treated group. Also, OPG gene expression was significantly higher in the ALN-treated group, compared to GIO group, control group and BMSCs-treated group. Also, BMSCs-treated group showed significant increase in OPG gene expression compared to GIO group but its level still lower than the control level. Conclusion: Bone regeneration through induction of BMSCs could promote osteogenesis and provide a rational therapeutic strategy for osteoporosis. However, new approach to increase the homing and retention of the BMSCs to bone is required to augment bone formation and increase bone mass for the treatment of osteoporosis.
[Hanan Fathy Al-Saeed and Ahmed Hashem Amin. Effect of Mesenchymal Stem Cells Systemic Implantation on Glucocorticoid- Induced Osteoporosis in Male Rats: A Comparative Study with Alendronate. J Am Sci 2012;8(10):641-650]. (ISSN: 1545-1003). http://www.jofamericanscience.org. 87
Keywords: glucocorticoid, osteoporosis, mesenchymal stem cells, osteoprotegerin, bone turnover markers. Full Text 87
