Aqueous extract of pomegranate seed attenuates glucocorticoid-induced bone loss and hypercalciuria in mice: A comparative study with alendronate.
The present study was performed in order to examine bone loss and calcium homeostasis in mice with glucocorticoid (GC)-induced osteoporosis (GIOP) following treatment with the aqueous extract of pomegranate seed (AE-PS). In addition, a comparative study with alendronate was performed. Biomarkers in the serum and the urine were measured. The tibias, kidney and duodenum were removed in order to measure the levels of bone calcium, protein expression as well as to perform histomorphological analysis of the bone. GC treatment facilitated the induction of hypercalciuria in the mice, and the AE-PS‑treated mice exhibited a greater increase in serum calcium and a decrease in urine calcium. The AE-PS reversed the deleterious effects on the trabecular bone induced by DXM and stimulated bone remodeling, including an increase in bone calcium and alkaline phosphatase‑b (ALP-b) and a decrease in a the critical bone resorption markers C-terminal telopeptide of type I collagen (CTX) and tartrate‑resistant acid phosphatase-5b (TRAP-5b). Hematoxylin and eosin (H&E) staining revealed the increased disconnections and separation between the growth plate and the trabecular bone network as well as the reduction in the trabecular bone mass of the primary and secondary spongiosa throughout the proximal metaphysis of the tibia in the DXM group. Moreover, the decreased protein expression of transient receptor potential vanilloid (TRPV)5, TRPV6 and calbindin‑D9k (CaBP‑9k) was reversed by the AE-PS or alendronate supplementation in the kidneys and the duodenum as well as plasma membrane Ca2+‑ATPase1 (PMCA1) expression in the kidneys of mice with GIOP. There was no marked difference in pharmacological effectiveness between alendronate and the AE-PS. Taken together, these findings suggest that the AE-PS may be an alternative therapy suitable for use in the management of secondary osteoporosis.
Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, P.R. China.
Yan
Y
Zhang
Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, P.R. China.
Jin
J
Shao
Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, P.R. China.
Zhi
Z
Wang
Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, P.R. China.
Tieyi
T
Yang
Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, P.R. China.
Shuyi
S
Liu
Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, P.R. China.
Yue
Y
Liu
Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, P.R. China.
Xinbing
X
Fan
Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, P.R. China.
Weiguang
W
Ye
D019386:Alendronate / Q000627:therapeutic use*; D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002118:Calcium / Q000097:blood / Q000652:urine; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005938:Glucocorticoids / Q000009:adverse effects*; D053565:Hypercalciuria / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D029561:Lythraceae / Q000737:chemistry*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D053244:Osteoprotegerin / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D053245:RANK Ligand / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D012639:Seeds / Q000737:chemistry*; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013977:Tibia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014867:Water / Q000737:chemistry*
D005938:Glucocorticoids; D026901:Membrane Transport Proteins; D053244:Osteoprotegerin; D010936:Plant Extracts; D053245:RANK Ligand; D044169:Receptors, Calcium-Sensing; D014867:Water; D013739:Testosterone; D000071681:Tartrate-Resistant Acid Phosphatase; D002118:Calcium; D019386:Alendronate