Effects of human parathyroid hormone on bone morphogenetic protein signal pathway following spinal fusion in diabetic rats.
Osteoporosis is a major complication in patients with diabetes mellitus. Thus, it is crucial to study the signal mechanisms responsible for enhancement of bone mass in diabetes. Administration of human parathyroid hormone (hPTH) has been reported to prevent osteoblast apoptosis and have anabolic effects on bone in animals and humans. In the present study, we examined the effects of hPTH on expression of bone morphogenetic protein type 2 (BMP-2) and its receptor BMPR2 in diabetic rats following spinal fusion. Our data show that hPTH amplified BMP-2 and BMPR2 in bone tissues of non-diabetic rats, but not in diabetic rats. Our data further demonstrate that hPTH plays a role in regulating BMP-2 and BMPR2 via mTOR-PI3K signal pathway. We suggest specific signaling pathways by which hPTH regulates BMP-2 via mTOR-PI3K mechanism in bone formation following spinal fusion. Notably, our data indicate under diabetic conditions this signal pathway is impaired, thereby likely affecting bone formation after spinal fusion. The subsequent induction of BMP-2 and BMPR2 are likely a part of the protective effects aimed at attenuating pathological bone damage as a result of diabetes.
Department of Orthopedics, the Second Hospital of Shandong University, Jinan, Shandong, China.
S Q
SQ
Wu
Department of Orthopedics, the Second Hospital of Shandong University, Jinan, Shandong, China.
S Z
SZ
Ma
Department of Orthopedics, the Second Hospital of Shandong University, Jinan, Shandong, China.
C
C
Zhang
Department of Orthopedics, the Second Hospital of Shandong University, Jinan, Shandong, China.
D Q
DQ
Li
Department of Orthopedics, the Second Hospital of Shandong University, Jinan, Shandong, China.
C Z
CZ
Gao
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010281:Parathyroid Hormone / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013123:Spinal Fusion; D013311:Streptozocin; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D013904:Thoracic Vertebrae / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery
D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D052006:Bone Morphogenetic Protein Receptors, Type II; D010281:Parathyroid Hormone; D019869:Phosphatidylinositol 3-Kinases; D013311:Streptozocin; D058570:TOR Serine-Threonine Kinases; C525720:Bmp2 protein, rat; C546845:mTOR protein, rat; C498220:Bmpr2 protein, rat