Expression of TGF-β1 in the blood during fracture repair in an estrogen-deficient rat model

Abstract

OBJECTIVES:Previous studies have reported that osteoporosis due to estrogen deficiency influences fracture healing. Transforming growth factor (TGF-β) has been found to be involved in fracture healing via the regulation of the differentiation and activation of osteoblasts and osteoclasts. The current study aimed to determine the effects of estrogen on the expression of TGF-β1 during fracture healing in ovariectomized rats.METHODS:Thirty female Sprague-Dawley rats weighing 200–250 g were assigned to: (i) a sham-operated group that was given a normal saline; (ii) an ovariectomized control group that was given a normal saline; or (iii) an ovariectomized + estrogen (100 µg/kg/day) group that was treated with conjugated equine estrogen. The right femur of all rats was fractured, and a Kirschner wire was inserted six weeks post-ovariectomy. Treatment with estrogen was given for another six weeks post-fracture. At the end of the study, blood samples were taken, and the right femur was harvested and subjected to biomechanical strength testing.RESULTS:The percentage change in the plasma TGF-β1 level before treatment was significantly lower in the ovariectomized control and estrogen groups when compared with the sham group (p<0.001). After six weeks of treatment, the percentage change in the plasma TGF-β1 level in the estrogen group was significantly higher compared with the level in the ovariectomized control group (p = 0.001). The mean ultimate force was significantly increased in the ovariectomized rats treated with estrogen when compared with the ovariectomized control group (p = 0.02).CONCLUSION:These data suggest that treatment with conjugated equine estrogen enhanced the strength of the healed bone in estrogen-deficient rats by most likely inducing the expression of TGF-β1.

Transforming Growth Factor β1 (TGF-β1) in the Sera of Postmenopausal Osteoporotic Females

“…Our observation opposes the results of several studies that have reported TGF-β1 has a protective role against osteoporosis and aids bone healing (3-5, 7, 11, 22). However, there are several other studies consistent with our results.…”

“…The transforming growth factor (TGF)-β molecules are a super family of cytokines, including TGF-β, bone morphogenetic proteins (BMPs) and activins, which regulate the growth and differentiation of osteoblasts and osteoclasts (5). The TGF-β1, TGF-β2 and TGF-β3 are closely related mammalian isoforms, with TGF-β1 being the most abundant isoform in the bone (6).…”

“…In a study conducted by Akinci et al (15) on males with osteoporosis, they demonstrated that TGF-β1 level is decreased in the sera of these cases. In a rat model, Estai et al (5) suggested that treatment with estrogen improved the strength of the bone in estrogen-deficient rats by inducing the expression of TGF-β1. In another study by Kim et al (16), it was implied that TGF-β1 positively inhibits bone resorption in rats.…”

Associations of SAA1 gene polymorphism with Lipid lelvels and osteoporosis in Chinese women

“…Some metabolic changes, such as those that occur due to a lack of estrogen, immobilization, metabolic acidosis, hyperparathyroidism, and systemic and local inflammatory diseases, affect the osteoclast count and activity associated with bone turnover [13]. Prostaglandins, insulin-like growth factors (IGFs), interleukins (IL-1, IL-6, and IL-11), tumor necrosis factor (TNF), and several local factors in bone, such as transforming growth factor (TGF), also contribute to the regulation of bone formation and resorption [13,14]. …”

Prolonged alendronate treatment prevents the decline in serum TGF-β1 levels and reduces cortical bone strength in long-term estrogen deficiency rat model

“…The P-6 MSCs were seeded either treated with alendronate (Ale, Sigma, St. Louis, MO) at 10 −10 -10 −6 M for 6 hours or cultured in osteogenic medium that contained alendronate. RNA was collected from the cultures at 6 hours, day 3, 7 and 14 to perform real-time reverse transcript PCR (RT-PCR) for genes encoding proteins in TGF-β1signaling pathway ( TGF -β 1, Smad2 and Smad3 ) and markers of osteoblast differentiation ( Runx2 ), maturation (osteocalcin, Bglap ) or mineralization (osteopontin, Opn ) [42–44]. …”