Search

It is not clear as to whether weight bearing and ambulation may affect bone growth. Our goal was to study the role of mechanical loading (one of the components of ambulation) on endochondral ossification and longitudinal bone growth. Thus, we applied cyclical, biologically relevant strains for a prolonged time period (4 weeks) to one tibia of juvenile mice, while using the contralateral one as an internal control. By the end of the 4‐week loading period, the mean tibial growth of the loaded tibiae was significantly greater than that of the unloaded tibiae. The mean height and the mean area of the loaded tibial growth plates were greater than those of the unloaded tibiae. In addition, in female mice we found a greater expression of PTHrP in the loaded tibial growth plates than in the unloaded ones. Lastly, microCT analysis revealed no difference between loaded and unloaded tibiae with respect to the fraction of bone volume relative to the total volume of the region of interest or the tibial trabecular bone volume. Thus, our findings suggest that intermittent compressive forces applied on tibiae at mild–moderate strain magnitude induce a significant and persistent longitudinal bone growth. PTHrP expressed in the growth plate appears to be one growth factor responsible for stimulating endochondral ossification and bone growth in female mice. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of the dosage and duration of fluoride and aluminum(F and Al) co-exposure on the skeletal growth and bone quality of juvenile rats. Forty-eight 8-week-old Sprague-Dawley rats were randomly assigned to normal control, low F and Al exposure, and high F and Al exposure groups, with 45-day and 90-day subgroups established for each. We measured body length, tibia length, conducted bone histomorphometric analysis of the proximal tibia, performed micro-CT scans and three-point bending tests of the femur. Compared to the age-matched control group, the low F and Al group at 45 days exhibited increased bone formation and stiffness; the low F and Al group at 90 days and the high F and Al group at 45 days showed increases in body length, tibia length, growth plate width, longitudinal bone growth rate, bone turnover, and improved microstructure. Notably, bone elastic stress only elevated in the high F and Al group at 45 days. Conversely, the high F and Al exposure group at 90 days experienced decreases in the aforementioned parameters, with the exception of growth plate width, and displayed abnormal hypertrophic chondrocyte morphology in the growth plate. In summary, long-term exposure to low levels of F and Al and short-term exposure to high levels of F and Al promote bone formation followed by bone resorption in juvenile rats, stimulating bone growth and enhancing bone quality. However, long-term exposure to high levels F and Al results in low bone turnover, slow bone growth, and reduced bone property.

Approximately 80% of children with short stature are classified as having Idiopathic Short Stature (ISS). While growth hormone (GH) treatment received FDA approval in the United States in 2003, its long-term impact on final height remains debated. Other treatments, like aromatase inhibitors, metformin, and insulin-like growth factor-1 (IGF-1), have been explored, but there is no established standard treatment for ISS. In South Korea and other Asian countries, East Asian Traditional Medicine (EATM) is sometimes employed by parents to potentially enhance their children's height growth, often involving herbal medicines. One such product, Astragalus membranaceus extract mixture HT042, claims to promote height growth in children and has gained approval from the Korean Food and Drug Administration (KFDA). Research suggests that HT042 supplementation can increase height growth in children without skeletal maturation, possibly by elevating serum IGF-1 and IGF-binding protein-3 levels. Preclinical studies also indicate the potential benefits of natural products, including of EATM therapies for ISS. The purpose of this review is to offer an overview of bone growth factors related to ISS and to investigate the potential of natural products, including herbal preparations, as alternative treatments for managing ISS symptoms, based on their known efficacy in in vivo studies. [ABSTRACT FROM AUTHOR]

Previous studies have reported that collagen tripeptide (CTP) derived from collagen hydrolysate has various beneficial effects on health by protecting against skin aging and improving bone formation and cartilage regeneration. Collagen-Tripep20TM (CTP20), which is a low-molecular-weight CTP derived from fish skin, contains a bioactive CTP, Gly-Pro-Hyp >3.2% with a tripeptide content >20%. Herein, we investigated the osteogenic effects and mechanisms of CTP20 (<500 Da) on MG-63 osteoblast-like cells and SW1353 chondrocytes. And we measured promoting ratio of the longitudinal bone growth in childhood rats. First, CTP20 at 100 μg/mL elevated the proliferation (15.0% and 28.2%), alkaline phosphatase activity (29.3% and 32.0%), collagen synthesis (1.25- and 1.14-fold), and calcium deposition (1.18- and 1.15-fold) in MG-63 cells and SW1353, respectively. In addition, we found that CTP20 could promote the longitudinal growth and height of the growth plate of the tibia in childhood rats. CTP20 enhanced the protein expression of insulin-like growth factor-1 (IGF-1) in MG-63 and SW1353 cells, and in the growth plate of childhood rats, along with Janus Kinase 2, and signal transducer and activator of transcription 5 activation in MG-63 and SW1353 cells. CTP20 also elevated the expression levels of bone morphogenetic proteins (BMPs) in MG-63 and SW1353 cells and in the growth plates of childhood rats. These results indicate that CTP20 may promote the endochondral ossification and longitudinal bone growth, through enhancing of IGF-1 and BMPs. (Clinical Trial Registration number: smecae 19-09-01). [ABSTRACT FROM AUTHOR]

Tachypleus tridentatus (T. tridentatus) is a marine animal and traditional Chinese medicine. T. tridentatus plasma is a valuable resource for important medical and health-based functions. In this experiment, in order to evaluate the effect and mechanism of T. tridentatus plasma with respect to the promotion of bone tissue growth in rats, the processes of ultrafiltration and mass spectrometry were first used to separate and identify the components of T. tridentatus plasma. Then, a comparison of the effects of the T. tridentatus plasma samples, which each possessed different molecular weights, regarding the growth of the long bones of rats was conducted. Finally, transcriptomics, proteomics, and bioinformatics were all used to analyze the biological functions and related signaling pathways of the T. tridentatus plasma in order to promote rat bone growth. The results showed that the contents of amino acid residues in peptides are related to the growth promotion that was contained in the 10–30 kDa plasma group. Moreover, the T. tridentatus plasma samples were found to be higher in this respect than those in the whole plasma group. In addition, the 10–30 kDa plasma group could significantly promote bone growth activity in rats. The proteomic analysis showed that the proteins that were differentially expressed in the 10–30 kDa plasma group were mainly enriched in the PI3K-AKT signal pathway. Our study suggested that the T. tridentatus plasma possesses promising potential for the purposes of clinical use, whereby it can serve the role of a growth-promoting agent. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of the dosage and duration of fluoride and aluminum(F and Al) co-exposure on the skeletal growth and bone quality of juvenile rats. Forty-eight 8-week-old Sprague-Dawley rats were randomly assigned to normal control, low F and Al exposure, and high F and Al exposure groups, with 45-day and 90-day subgroups established for each. We measured body length, tibia length, conducted bone histomorphometric analysis of the proximal tibia, performed micro-CT scans and three-point bending tests of the femur. Compared to the age-matched control group, the low F and Al group at 45 days exhibited increased bone formation and stiffness; the low F and Al group at 90 days and the high F and Al group at 45 days showed increases in body length, tibia length, growth plate width, longitudinal bone growth rate, bone turnover, and improved microstructure. Notably, bone elastic stress only elevated in the high F and Al group at 45 days. Conversely, the high F and Al exposure group at 90 days experienced decreases in the aforementioned parameters, with the exception of growth plate width, and displayed abnormal hypertrophic chondrocyte morphology in the growth plate. In summary, long-term exposure to low levels of F and Al and short-term exposure to high levels of F and Al promote bone formation followed by bone resorption in juvenile rats, stimulating bone growth and enhancing bone quality. However, long-term exposure to high levels F and Al results in low bone turnover, slow bone growth, and reduced bone property. • The co-exposure of fluoride and aluminum exhibits a dual effect, initially promoting and then inhibiting the functions of osteoblasts, osteoclasts, and chondrocytes. • Bone formation responds to fluoride and aluminum intake before resorption, with changes in resorption positively correlating to formation. • The co-exposure of fluoride and aluminum initially increases but subsequently inhibits or worsens the growth of long bones and bone quality in juvenile rats. [ABSTRACT FROM AUTHOR]

Tachypleus tridentatus (T. tridentatus) is a marine animal and traditional Chinese medicine. T. tridentatus plasma is a valuable resource for important medical and health-based functions. In this experiment, in order to evaluate the effect and mechanism of T. tridentatus plasma with respect to the promotion of bone tissue growth in rats, the processes of ultrafiltration and mass spectrometry were first used to separate and identify the components of T. tridentatus plasma. Then, a comparison of the effects of the T. tridentatus plasma samples, which each possessed different molecular weights, regarding the growth of the long bones of rats was conducted. Finally, transcriptomics, proteomics, and bioinformatics were all used to analyze the biological functions and related signaling pathways of the T. tridentatus plasma in order to promote rat bone growth. The results showed that the contents of amino acid residues in peptides are related to the growth promotion that was contained in the 10–30 kDa plasma group. Moreover, the T. tridentatus plasma samples were found to be higher in this respect than those in the whole plasma group. In addition, the 10–30 kDa plasma group could significantly promote bone growth activity in rats. The proteomic analysis showed that the proteins that were differentially expressed in the 10–30 kDa plasma group were mainly enriched in the PI3K-AKT signal pathway. Our study suggested that the T. tridentatus plasma possesses promising potential for the purposes of clinical use, whereby it can serve the role of a growth-promoting agent.

Longitudinal bone growth mainly occurs during adolescence and can be enhanced by growth hormones. We hypothesized that water extracts from roots of Allium fistulosum L. (Welsh onion, WO; 15 or 45 mg/kg bw/day) and Portulaca oleracea L. (PO; 15 or 45 mg/kg bw/day) can stimulate longitudinal bone growth in weanling male rats for 4 weeks. Femur and tibia lengths were higher in the WO-H and PO-H groups than in the control. The proliferative and hypertrophic zones of the growth plate were greater in the legs of WO-H and PO-H rats than in the control; a similar increase was observed in the positive-control (growth hormone, 20 μg/kg bw/day). WO-H and PO-H treatments were found to potentiate insulin-like growth factor-1 (IGF-1) signaling (pIRS-2 → pAkt) in MG-63 osteoblasts compared to control. WO-H and PO increased cell proliferation possibly by activating transforming growth factor (TGF)-β signaling via elevated BMP-2 and Smad4 expression in MG-63 cells. In conclusion, WO and PO are potential to promote the proliferation of the leg growth plate similar to growth hormone.

Previously, we reported that the administration of a mixture of Humulus japonicus (MH) increased the longitudinal bone growth rate in Sprague Dawley rats. In this study, we investigated the effects of the dietary administration of MH on longitudinal bone growth in growth hormone (GH)-deficient hypophysectomized male and female rats to determine whether the effect of MH was similar to that of GH. We measured the nose-to-anus and nose-to-tail length gain, femur and tibia lengths, growth plate zones, and expression of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) after the dietary administration of MH or the injection of GH into hypophysectomized rats for 4 weeks. Results demonstrated that the dietary administration of MH had no effect on longitudinal bone growth, whereas the injection of GH increased the nose-to-tail length gain and femur and tibia lengths in hypophysectomized rats. In addition, MH did not affect the growth plate, bone mineralization, and expression of IGF-1 and IGFBP-3. These findings indicate that MH does not exert a GH-like effect and that the effects of MH and GH on longitudinal bone growth involve different pathways. [ABSTRACT FROM AUTHOR]

Abstract Background Yukmijihwangtang (YJT) is a traditional Korean medicine that has been used to treat kidney-yin deficiency symptoms such as dizziness and tinnitus. In addition, because it is also thought to nourish kidney-yin, it has been used to treat short stature from congenital deficiency. This study evaluated the effects of YJT on longitudinal bone growth in rats. Methods Female adolescent rats were randomly assigned to groups that received distilled water (per os [p.o.] twice a day; control), recombinant human growth hormone (rhGH; 20 μg/kg, subcutaneous [s.c.] once a day), or two different doses of YJT (100 or 300 mg/kg, p.o. twice a day). In each group, treatment was maintained for 4 days. Rats were injected intraperitoneally with 5-bromo-2’-deoxyuridine (BrdU; 50 mg/kg) to label proliferating chondrocytes on days 2 – 4. Tetracycline hydrochloride (20 mg/kg) was injected intraperitoneally to form fluorescent bands on the growth plates on day 3 for measuring the longitudinal bone growth rate. Expression of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in the growth plate was identified using immunohistochemistry. Results There was a significant increase in the rate of bone growth in the 300 mg/kg YJT group (523.8 ± 23.7 μm/day; P

• Welsh onion (WO-H) and Portulaca oleracea (PO-H) increased femur and tibia lengths compared to the control in young rats. • The proliferative and hypertrophic zones of the growth plate were greater in the legs of WO-H and PO-H rats. • WO-H and PO-H reduced insulin resistance and PO-H had a better effect on it than the growth hormone injection. • WO-H and PO-H potentiated IGF-1 (pIRS-2 → pAkt) and TGF-β signaling in osteoblasts. • Longitudinal bone growth is associated with the improvement of insulin sensitivity. Longitudinal bone growth mainly occurs during adolescence and can be enhanced by growth hormones. We hypothesized that water extracts from roots of Allium fistulosum L. (Welsh onion, WO; 15 or 45 mg/kg bw/day) and Portulaca oleracea L. (PO; 15 or 45 mg/kg bw/day) can stimulate longitudinal bone growth in weanling male rats for 4 weeks. Femur and tibia lengths were higher in the WO-H and PO-H groups than in the control. The proliferative and hypertrophic zones of the growth plate were greater in the legs of WO-H and PO-H rats than in the control; a similar increase was observed in the positive-control (growth hormone, 20 μg/kg bw/day). WO-H and PO-H treatments were found to potentiate insulin-like growth factor-1 (IGF-1) signaling (pIRS-2 → pAkt) in MG-63 osteoblasts compared to control. WO-H and PO increased cell proliferation possibly by activating transforming growth factor (TGF)-β signaling via elevated BMP-2 and Smad4 expression in MG-63 cells. In conclusion, WO and PO are potential to promote the proliferation of the leg growth plate similar to growth hormone. [ABSTRACT FROM AUTHOR]

Abstract The effects of dietary supplementation with Antarctic krill oil (AKO) on longitudinal bone growth in adolescent male Institute for Cancer Research (ICR) mice for 21 days were investigated. Histological results showed that AKO promoted longitudinal bone growth, increased skeletal mineral content and strength, enhanced entochondrostosis supported by higher longitudinal bone growth rate and growth plate height. Then, the potential mechanisms responsible for these observations were measured, results showed that AKO increased the secretion of the GH-IGF-1 pathway and entochondrostosis-related factors in serum increased the expression of IGF-1 in the liver and bone, which promoted proliferation and differentiation of chondrocytes, vascular invasion and bone formation related gene expression. AKO promoted longitudinal bone growth, using the GH-IGF-1 pathway, suggesting that AKO might be a potential functional food to improve growth potential of adolescents. Graphical abstract Image 1 Highlights • Intake of Antarctic krill oil (AKO) greatly increased longitudinal bone growth. • AKO increased proliferative and hypertrophic zone heights in growth plate. • AKO increased the process of entochondrostosis. • AKO regulated bone growth of adolescent mice using the GH-IGF-1 pathway. [ABSTRACT FROM AUTHOR]

Abstract Objective Growth hormone (GH) regulates both longitudinal growth and bone acquisition in children, and has profound metabolic effects. The aim was to investigate the association between proteomic biomarkers, body fat, nutrition and bone formation markers, and longitudinal growth in response to GH during the first year of treatment. The degree to which changes in these factors could explain variations in GH-dependent longitudinal growth and bone mineralization was also assessed. Methods The individualized GH dose trial included 128 short prepubertal children with either normal (non-GH-deficient) or reduced levels of GH secretion (GH-deficient) (mean age ± SD, 8.6 ± 2.6 years; 90 boys), i.e., with a broad range of GH-secretion and GH-responsiveness, receiving GH treatment (mean 43 μg/kg/day). Blood samples were taken and dual-energy X-ray absorptiometry (DXA) measured at baseline and 1 year of treatment. Step-wise multiple regression models were constructed including three steps with different independent variables added at each step to explain the variance in outcome variables (height SDS , bone mineral content (BMC) and bone mineral density (BMD). Independent variables included in Step I were previously identified proteomic markers related to GH treatment response, bone formation markers (intact PINP, bone-specific alkaline phosphatase and osteocalcin), variables at treatment start (GH dose mU/kg/day, GH maximum secretion, and difference between child's current and mid-parental height SDS). Step II explored the added influence of body composition data (body mass index or DXA). Step III explored the added influence of serum nutritional markers and hormones. Results Step I variables explained 71% of the variation in first year height SDS gain, median (minimum–maximum) 0.8 (0.24–1.67); and the proportion explained rose to 73% following inclusion of step II variables and 75% following step III. Corresponding values for total body BMC were 58%, 78%, and 80%, respectively. Proportions fell by approximately 20% when BMC was adjusted for height; 33%, 57%, and 57% for steps I, II, and III, respectively. Corresponding values for total body BMD were 29%, 39%, and 45%, respectively. Conclusion For total BMC, as much as 80% of the variation during the first year of GH treatment could be explained by proteomic biomarkers, body fat, nutrition and bone formation markers, whereas for height-adjusted BMC 57% could be explained. The inclusion of information about either body composition (fat/lean mass) or nutritional markers contributed with approximately 20%. The variation in height SDS gain could be explained to 75%. Hence, information of fat or nutrition markers was needed for explaining the variation in bone acquisition to the same magnitude as explaining the variation in height response. Highlights • Proteomic biomarkers, body composition, nutrition and bone formation were associated with bone growth and mineralization. • Variations in height SDS gain and total BMC during the first year of GH were explained to 75% and 80%, respectively. • Variations in first-year gain in BMD and in height-adjusted BMC were explained to 45% and 57%, respectively. • Fat/nutrition markers were needed to explain variation in bone acquisition to the same magnitude as height response. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is much more detrimental to bone than previously thought. Specifically, it is associated with aberrant bone remodeling, defective bone microstructure, poor bone quality, and growth retardation. The T2DM-associated impairment of bone elongation may result from a decrease in growth plate function, but the detailed mechanism has been unknown. The present study, therefore, aimed to test hypothesis that T2DM led to premature apoptosis of growth plate chondrocytes in Goto–Kakizaki (GK) type 2 diabetic rats, and thus triggered the compensatory responses to overcome this premature apoptosis, such as overexpression of Runt -related transcription factor (Runx)-2 and vascular endothelial growth factor (VEGF), the essential mediators for bone elongation. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) of epiphyseal sections successfully revealed increases in chondrocyte apoptosis in the hypertrophic zone (HZ) and chondro-osseous junction of GK rats. Quantitative immunohistochemical analysis further confirmed the overexpression of parathyroid hormone-related protein (PTHrP), Runx2 and VEGF, but not Indian hedgehog (Ihh) in the HZ. Analysis of blood chemistry indicated suppression of bone remodeling with a marked decrease in parathyroid hormone level. In conclusion, GK rats manifested a premature increase in chondrocyte apoptosis in the HZ of growth plate, and a compensatory overexpression of chondroregulatory proteins, such as PTHrP, Runx2, and VEGF. Our results, therefore, help explain how T2DM leads to impaired bone elongation and growth retardation. [ABSTRACT FROM AUTHOR]

HT042 is a new herbal prescription consisting of Astragalus membranaceus, Phlomis umbrosa and Eleutherococcus senticosus, which are used in Korean medicine to stimulate growth in children. We investigated the effects of HT042 on the body weight, longitudinal bone growth, and bone length in spontaneous dwarf rats (SDR). Male and female SDRs were divided into three groups: the control group (DW, 10 mL/kg/day), the recombinant human GH group (rhGH; 500 μg/kg/day), and the HT042 (100 mg/kg/day) group. Each group received the respective treatments for 10 days. Body weight was measured on day 10 of treatment. On day 8, tetracycline (20 mg/kg) was injected intraperitoneally into all individuals to form a fluorescent band on the newly synthesized bone. On day 10, femur and tibia lengths were measured using PIXImus. Body weight, longitudinal bone growth, and bone length were not affected in the HT042 group. In contrast, the rhGH group showed significantly increased body weight, longitudinal bone growth, and bone length. In conclusion, HT042 does not act through a GH-like effect to promote longitudinal bone growth. [ABSTRACT FROM AUTHOR]

Abstract: Growth plates are spatially polarized and structured into three histologically and functionally distinct layers—the resting zone (RZ), proliferative zone (PZ), and hypertrophic zone (HZ). With age, growth plates undergo functional and structural senescent changes including declines of growth rate, proliferation rate, growth plate height and cell number. To explore the mechanisms responsible for spatially-associated differentiation and temporally-associated senescence of growth plate in an unbiased manner, we used microdissection to collect individual growth plate zones from proximal tibiae of 1-week rats and the PZ and early hypertrophic zones of growth plates from 3-, 6-, 9-, and 12-week rats and analyzed gene expression using microarray. We then used bioinformatic approaches to identify significant changes in biological functions, molecular pathways, transcription factors and also to identify specific gene products that can be used as molecular markers for individual zones or for temporal development. [Copyright &y& Elsevier]

In this review we summarize available data regarding linear growth in oestrogen receptor alpha (ERα)- and oestrogen receptor beta (ERβ)-deficient mice. We discuss these findings in relation to known oestrogenic effects in humans and the possibility of applying this knowledge for the therapeutic modulation of longitudinal bone growth employing selective oestrogen receptor modulators (SERMs). We conclude that SERMs potentially could offer new possibilities to modulate bone growth by specifically targeting different oestrogen receptors within the growth plate. [ABSTRACT FROM AUTHOR]

Longitudinal bone growth occurs at the growth plate by endochondral ossification. Within the growth plate, chondrocyte proliferation, hypertrophy, and cartilage matrix secretion result in chondrogenesis. The newly formed cartilage is invaded by blood vessels and bone cells that remodel the newly formed cartilage into bone tissue. This process of longitudinal bone growth is governed by a complex network of endocrine signals, including growth hormone, insulin-like growth factor I, glucocorticoid, thyroid hormone, estrogen, androgen, vitamin D, and leptin. Many of these signals regulate growth plate function, both by acting locally on growth plate chondrocytes and also indirectly by modulating other endocrine signals in the network. Some of the local effects of hormones are mediated by changes in paracrine factors that control chondrocyte proliferation and differentiation. Many human skeletal growth disorders are caused by abnormalities in the endocrine regulation of the growth plate. This review provides an overview of the endocrine signals that regulate longitudinal bone growth, their interactions, and the mechanisms by which they affect growth plate chondrogenesis. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In mammals, longitudinal bone growth occurs rapidly in prenatal and early postnatal life, but then slows and eventually ceases. This deceleration, which reflects a decline in chondrocyte proliferation, was previously attributed to a hormonal or other systemic mechanism. However, new evidence suggests that it is due to a local mechanism within the growth plate. In particular, recent findings suggest that growth plate chondrocytes have a finite proliferative capacity that is gradually exhausted, causing growth to slow and finally stop. This concept has provided insight into clinical phenomena including catch-up growth after transient growth inhibition, catch-down growth after transient estrogen exposure, and epiphyseal fusion. [ABSTRACT FROM AUTHOR]

The growth plate is a specialized structure that is responsible for longitudinal bone growth (LGR). Growth plate organization is altered with loading in rats. Parathyroid hormone (PTH) is known to induce mitogenic effect on chondrocytes in vitro. Type I PTH/PTH related peptide (rP) receptor is expressed in growth plate cartilage in rats. We therefore investigated the effect of PTH administration on the organization and longitudinal growth rate of the growth plate in rats. We also investigated the effect of PTH on the changes induced by unloading in the organization and growth of the growth plate. Thirty 6-week-old and 30 15-week-old male Sprague-Dawley rats were randomly assigned to five groups ( n = 6 per group), i.e., basal controls, control (i.e., normally loaded), PTH-treated control (i.e., PTH-treated under normal loading), unloaded, and PTH-treated under unloading. PTH-treated animals received human PTH (1–34) at a dose of 80 μg/kg per day five times per week for 3 weeks, for the duration of unloading. In young loaded rats treated with the systemic administration of PTH, growth plate thickness, chondrocyte number, and LGR were increased in the proximal tibiae compared with findings in young loaded rats without PTH administration. Hindlimb unloading induced a reduction in growth plate thickness, chondrocyte number, and LGR. In young rats, systemic administration of PTH partly prevented these changes induced by unloading. These preventive effects of PTH were observed only in young rats; not in adult rats. These results show that the systemic administration of PTH stimulates longitudinal bone growth, and diminishes the reduction in growth plate growth induced by unloading in young rats. [ABSTRACT FROM AUTHOR]

We have studied the effect of local arterial infusion of bacterially produced human growth hormone (hGH), insulinlike growth factor I (IGF-I), or pituitary-derived ovine prolactin (oPRL) on longitudinal bone growth of hypophysectomized rats. The substances were infused during a 14-day period by osmotic mini-pumps through a catheter which was implanted into the femoral artery of one hindlimb. Longitudinal bone growth was measured by the intravital marker tetracycline. Infusion of 1 microgram hGH per day stimulated bone growth only of the treated limb and not of the uninfused contralateral limb. Infusion of 10 micrograms hGH per day also stimulated unilateral longitudinal bone growth, but the uninfused contralateral limb also showed a significant growth response, probably because local administration of GH at this dose caused a significant elevation of GH in the systemic circulation. As a result, the differential growth response between the GH-treated and untreated limbs decreased compared to rats that were infused with 1 microgram hGH per day. Unilateral arterial infusion of 5 micrograms human IGF-I or 10 micrograms oPRL per day did not produce a significant growth response. The results of the present study confirm the observation by Schlechter and co-workers, who demonstrated that unilateral arterial infusion of GH maintained tibial cartilage width following hypophysectomy in the rat. The results of Schlechter and coworkers and the results of the present study show that GH in vivo stimulates epiphyseal cartilage growth directly. However, an increased local production of insulinlike growth factors is probably of importance for the expression of the direct effect of GH on longitudinal bone growth.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]