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Title:
The Peroxisome Proliferator Activator Receptor Alpha/Delta Agonists Linoleic Acid and Bezafibrate Upregulate Osteoblast Differentiation and Induce Periosteal Bone Formation In Vivo | Calcified Tissue International
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We showed previously that some actions of prostaglandin E2 (PGE2) on bone are caused by its degradation product, PGA2, which mediates its effects via a class of nuclear receptors known as the peroxisome proliferator activator receptors (PPARs), suggesting that the PPARs may be involved in the regulation of bone formation. The aims of this study were to determine the effects of PPARα/Γ agonists on bone in vitro and in vivo. PPAR agonists were examined in vitro using the fibroblastic colony-forming unit (CFU-f) assay. The PPARα/Γ agonists linoleic acid (LA) and bezafibrate (Bez) were then administered to intact male rats by daily s.c. injection for 12 weeks with either vehicle (10% dimethyl sulfoxide), LA (0.3 mg/kg), or Bez (1 mg/kg). CFU-f assays were performed on stromal cells ex vivo. Bone mineral density (BMD) and serum markers of formation and resorption were measured. Bone histomorphometry was performed at cancellous and cortical bone sites. PPARα/Γ agonists increased significantly the number of osteoblastic colonies as demonstrated by increased alkaline phosphatase activity, collagen production, and calcification. This increase was typically equal to or greater than that achieved with the known bone anabolic agent PGE2. In intact male rats, LA and Bez increased metaphyseal BMD by 7% and 11%, respectively. Increased BMD was associated with an increase in total bone area, although no changes were observed in bone formation rate within the trabecular compartment. Serum osteocalcin and osteoprogenitor numbers were increased, whereas there was no change in either tartrate-resistant acid phosphatase 5b or osteoclast number. Both LA and Bez increased cortical bone area by approximately 38%, periosteal perimeter by 15%, and periosteal bone formation by 221% and 140%, respectively. There was no effect on medullary cavity area or endocortical perimeter. These data suggest that PPARα/Γ may have roles in bone anabolism, specifically in the regulation of periosteal bone formation. They are potential therapeutic targets for osteoporosis therapy.
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bone, article, pubmed, google, scholar, cas, formation, peroxisome, receptor, agonists, receptors, rats, tissue, acid, cells, increased, access, proliferatoractivated, privacy, cookies, content, journal, periosteal, prostaglandin, effects, scutt, data, area, publish, research, search, proliferator, activator, differentiation, vivo, october, nuclear, regulation, pparαΓ, cfuf, bez, male, marrow, calcif, int, information, log, linoleic, bezafibrate, karen,
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peroxisome proliferator-activated receptors peroxisome proliferatorāactivated receptors mineralizing fibroblast-colony-forming assays month download article/chapter fibroblastic colony-forming unit transcription factor pgc-1α pparalpha-leukotriene b4 pathway modeling-dependent bone gain retinoic acid receptor long-term daily administration nuclear receptor signaling pparα/Ī“ agonists related subjects full article pdf privacy choices/manage cookies periosteal bone formation bone formation rate total bone area nuclear receptor ppar agonists polyunsaturated fatty acids cortical bone sites ppar delta bone mineral density cancellous bone site low bone turnover european economic area medullary cavity area bone marrow cells potential therapeutic targets ke hz closed growth plate mc3t3-e1 preosteoblasts antidiabetic compound rosiglitazone journal finder publish conditions privacy policy osteoporosis therapy royal pharmaceutical society young rats increases nuclear receptors intact male rats aged male rats adult stem cells accepting optional cookies article log author information authors sheffield/sheffield children pparα/Ī“ inflammation control check access
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headline:The Peroxisome Proliferator Activator Receptor Alpha/Delta Agonists Linoleic Acid and Bezafibrate Upregulate Osteoblast Differentiation and Induce Periosteal Bone Formation In Vivo
description:We showed previously that some actions of prostaglandin E2 (PGE2) on bone are caused by its degradation product, PGA2, which mediates its effects via a class of nuclear receptors known as the peroxisome proliferator activator receptors (PPARs), suggesting that the PPARs may be involved in the regulation of bone formation. The aims of this study were to determine the effects of PPARα/Γ agonists on bone in vitro and in vivo. PPAR agonists were examined in vitro using the fibroblastic colony-forming unit (CFU-f) assay. The PPARα/Γ agonists linoleic acid (LA) and bezafibrate (Bez) were then administered to intact male rats by daily s.c. injection for 12 weeks with either vehicle (10% dimethyl sulfoxide), LA (0.3 mg/kg), or Bez (1 mg/kg). CFU-f assays were performed on stromal cells ex vivo. Bone mineral density (BMD) and serum markers of formation and resorption were measured. Bone histomorphometry was performed at cancellous and cortical bone sites. PPARα/Γ agonists increased significantly the number of osteoblastic colonies as demonstrated by increased alkaline phosphatase activity, collagen production, and calcification. This increase was typically equal to or greater than that achieved with the known bone anabolic agent PGE2. In intact male rats, LA and Bez increased metaphyseal BMD by 7% and 11%, respectively. Increased BMD was associated with an increase in total bone area, although no changes were observed in bone formation rate within the trabecular compartment. Serum osteocalcin and osteoprogenitor numbers were increased, whereas there was no change in either tartrate-resistant acid phosphatase 5b or osteoclast number. Both LA and Bez increased cortical bone area by approximately 38%, periosteal perimeter by 15%, and periosteal bone formation by 221% and 140%, respectively. There was no effect on medullary cavity area or endocortical perimeter. These data suggest that PPARα/Γ may have roles in bone anabolism, specifically in the regulation of periosteal bone formation. They are potential therapeutic targets for osteoporosis therapy.
datePublished:2008-10-04T00:00:00Z
dateModified:2008-10-04T00:00:00Z
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Peroxisome proliferator activator receptor
Bone formation
Osteoporosis
Periosteum
Biochemistry
general
Endocrinology
Orthopedics
Cell Biology
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description:We showed previously that some actions of prostaglandin E2 (PGE2) on bone are caused by its degradation product, PGA2, which mediates its effects via a class of nuclear receptors known as the peroxisome proliferator activator receptors (PPARs), suggesting that the PPARs may be involved in the regulation of bone formation. The aims of this study were to determine the effects of PPARα/Γ agonists on bone in vitro and in vivo. PPAR agonists were examined in vitro using the fibroblastic colony-forming unit (CFU-f) assay. The PPARα/Γ agonists linoleic acid (LA) and bezafibrate (Bez) were then administered to intact male rats by daily s.c. injection for 12 weeks with either vehicle (10% dimethyl sulfoxide), LA (0.3 mg/kg), or Bez (1 mg/kg). CFU-f assays were performed on stromal cells ex vivo. Bone mineral density (BMD) and serum markers of formation and resorption were measured. Bone histomorphometry was performed at cancellous and cortical bone sites. PPARα/Γ agonists increased significantly the number of osteoblastic colonies as demonstrated by increased alkaline phosphatase activity, collagen production, and calcification. This increase was typically equal to or greater than that achieved with the known bone anabolic agent PGE2. In intact male rats, LA and Bez increased metaphyseal BMD by 7% and 11%, respectively. Increased BMD was associated with an increase in total bone area, although no changes were observed in bone formation rate within the trabecular compartment. Serum osteocalcin and osteoprogenitor numbers were increased, whereas there was no change in either tartrate-resistant acid phosphatase 5b or osteoclast number. Both LA and Bez increased cortical bone area by approximately 38%, periosteal perimeter by 15%, and periosteal bone formation by 221% and 140%, respectively. There was no effect on medullary cavity area or endocortical perimeter. These data suggest that PPARα/Γ may have roles in bone anabolism, specifically in the regulation of periosteal bone formation. They are potential therapeutic targets for osteoporosis therapy.
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Peroxisome proliferator activator receptor
Bone formation
Osteoporosis
Periosteum
Biochemistry
general
Endocrinology
Orthopedics
Cell Biology
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