Abstract
This study aimed to investigate the effects of Phlomis umbrosa root on bone growth and growth mediators in rats. Female adolescent rats were administered P. umbrosa extract, recombinant human growth hormone or vehicle for 10 days. Tetracycline was injected intraperitoneally to produce a glowing fluorescence band on the newly formed bone on day 8, and 5-bromo-2′-deoxyuridine was injected to label proliferating chondrocytes on days 8–10. To assess possible endocrine or autocrine/paracrine mechanisms, we evaluated insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) or bone morphogenetic protein-2 (BMP-2) in response to P. umbrosa administration in either growth plate or serum. Oral administration of P. umbrosa significantly increased longitudinal bone growth rate, height of hypertrophic zone and chondrocyte proliferation of the proximal tibial growth plate. P. umbrosa also increased serum IGFBP-3 levels and upregulated the expressions of IGF-1 and BMP-2 in growth plate. In conclusion, P. umbrosa increases longitudinal bone growth rate by stimulating proliferation and hypertrophy of chondrocyte with the increment of circulating IGFBP-3. Regarding the immunohistochemical study, the effect of P. umbrosa may also be attributable to upregulation of local IGF-1 and BMP-2 expressions in the growth plate, which can be considered as a GH dependent autocrine/paracrine pathway.
Highlights
Short stature is defined as the height of an individual more than two standard deviation score (SDS) below the average height for an age, sex, and population group [1]
To assess the possible endocrine/paracrine mechanism whereby P. umbrosa exerts its growth-promoting effects, we evaluated the insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) or bone morphogenetic protein-2 (BMP-2) in response to P. umbrosa administration in either growth plate or serum
IGF-1was was more highly expressed in hypertrophic antigen-specific more highly expressed in hypertrophic zoneszones than the intensity of IGF-1 expression in proliferative and hypertrophic zone compared with control
Summary
Short stature is defined as the height of an individual more than two standard deviation score (SDS) below the average height for an age, sex, and population group [1]. In the case of ISS, the US FDA approved GH therapy in ISS children shorter than2.25 SDS in 2003 based on the evidence derived from two clinical studies [11,12], the average increase in final height attributable to GH therapy in children with ISS is just 3.5–7.5 cm (4–7 years) [11,13,14,15,16] In this case of ISS, the effect remains controversial because the estimated cost of GH therapy for adult height gain is about 10,000–20,000 dollars/cm [1,15]. Children’s pain due to daily injection and abuse of human GH to increase the height of children who are already of normal height are considered controversial [17,18] For these reasons, alternative oral growth stimulators with relatively low cost are currently being studied. (BMP-2) in response to P. umbrosa administration in either growth plate or serum
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