scholarly journals A Mixture of Humulus japonicus Increases Longitudinal Bone Growth Rate in Sprague Dawley Rats

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2625
Author(s):  
Ok-Kyung Kim ◽  
Jeong moon Yun ◽  
Minhee Lee ◽  
Soo-Jeung Park ◽  
Dakyung Kim ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Tail Length ◽  
Janus Kinase ◽  
Sprague Dawley ◽  
Plate Height ◽  
Longitudinal Bone Growth ◽  
Sd Rats ◽  
Humulus Japonicus ◽  
Igfbp 3

The aim of this study was to investigate the effects of administration of a mixture of Humulus japonicus (MH) on longitudinal bone growth in normal Sprague Dawley (SD) rats. We measured the femur and tibia length, growth plate area, proliferation of chondrocytes, and expression of insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3), and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) phosphorylation after dietary administration of MH in SD rats for four weeks. The nose–tail length gain and length of femur and tibia increased significantly in the group that received MH for a period of four weeks. We performed H&E staining and Bromodeoxyuridine/5-Bromo-2′-Deoxyuridine (BrdU) staining to examine the effect of dietary administration of MH on the growth plate and the proliferation of chondrocytes and found that MH stimulated the proliferation of chondrocytes and contributed to increased growth plate height during the process of longitudinal bone growth. In addition, serum levels of IGF-1 and IGFBP-3 and expression of IGF-1 and IGFBP-3 mRNAs in the liver and bone were increased, and phosphorylation of JAK2/STAT5 in the liver was increased in the MH groups. Based on these results, we suggest that the effect of MH on longitudinal bone growth is mediated by increased JAK2/STAT5-induced IGF-1 production.

scholarly journals Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth

Endocrinology ◽  
2015 ◽  
Vol 156 (7) ◽  
pp. 2541-2551 ◽  
Author(s):  
Shufang Wu ◽  
Wei Yang ◽  
Francesco De Luca
Keyword(s):  
Mrna Expression ◽  
Growth Plate ◽  
Molecular Mechanisms ◽  
Bone Growth ◽  
Janus Kinase ◽  
Bone Morphogenetic Protein 2 ◽  
Plate Height ◽  
Systemic Injection ◽  
Longitudinal Bone Growth ◽  
Growth Promoting

GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated TamCartIgf1rflox/flox mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. TamCartIgf1rflox/flox tamoxifen-treated mice [knockout (KO) mice] and their Igf1rflox/flox control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-κB p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects.

scholarly journals Effect of Clodronate Administration on the Structure of the Primary Spongiosa derived from the Growth Cartilage in Growing Rats

2019 ◽  
Vol 2 (1) ◽  
pp. 27-35
Author(s):  
Helena Gil-Peña ◽  
Ángela Fernández-Iglesias ◽  
Rocío Fuente ◽  
Laura Alonso-Duran ◽  
Fernando Santos ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Blue Staining ◽  
Growth Spurt ◽  
Alcian Blue Staining ◽  
Tartrate Resistant Acid Phosphatase ◽  
Sprague Dawley ◽  
Proliferating Cells ◽  
Longitudinal Bone Growth ◽  
Growth Plate Cartilage

The effect of the inhibition of the resorptive activity of osteoclastic cells induced by bisphosphonate treatment on the primary spongiosa derived from the calcified cartilage of the growth plate was studied. We focused our attention on the primary spongiosa because it is the initial trabecular bone network that is first formed directly from growth plate mineralized cartilaginous septa. The study was carried out in male Sprague-Dawley rats at the age of 35 days, coinciding with the prepubertal growth spurt, a stage characterized by the highest values for growth rate. Animals were classified in two groups, controls and rats treated with clodronate 60 mg/kg/day. Body weights and tibial length were measured. The rate of longitudinal bone growth was obtained by calceine labelling and the height of the growth plate cartilage was measured. Histochemical analysis included Alcian blue staining, detection of tartrate-resistant acid phosphatise (TRAP) activity, von Kossa staining for mineralization and immunolocalization of proliferating cells. Microscopic examination revealed numerous tartrate-resistant acid phosphatase (TRAP)-positive cells at the chondroosseous junction and associated with subchondral trabeculae in control rat and that clodronate treatment induced a marked reduction of these cells. Clodronate-treated rats presented thinner subchondral trabeculae that were more irregularly oriented and decreased cell proliferation in the primary spongiosa. Results obtained showed that changes induced by clodronate treatment has little effect on the activity of the growth plate cartilage, without a significant effect on longitudinal bone growth even at doses much higher than those used in clinical practice.

scholarly journals The role of estrogen receptor-α and its activation function-1 for growth plate closure in female mice

2012 ◽  
Vol 302 (11) ◽  
pp. E1381-E1389 ◽  
Author(s):  
A. E. Börjesson ◽  
S. H. Windahl ◽  
E. Karimian ◽  
E. E. Eriksson ◽  
M. K. Lagerquist ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Growth Plate ◽  
Bone Growth ◽  
High Dose ◽  
Plate Height ◽  
Chondrocyte Proliferation ◽  
Growth Plates ◽  
Longitudinal Bone Growth ◽  
Female Mice

High estradiol levels in late puberty induce growth plate closure and thereby cessation of growth in humans. In mice, the growth plates do not fuse after sexual maturation, but old mice display reduced longitudinal bone growth and high-dose estradiol treatment induces growth plate closure. Estrogen receptor (ER)-α stimulates gene transcription via two activation functions (AFs), AF-1 and AF-2. To evaluate the role of ERα and its AF-1 for age-dependent reduction in longitudinal bone growth and growth plate closure, female mice with inactivation of ERα (ERα−/−) or ERαAF-1 (ERαAF-10) were evaluated. Old (16- to 19-mo-old) female ERα−/− mice showed continued substantial longitudinal bone growth, resulting in longer bones (tibia: +8.3%, P < 0.01) associated with increased growth plate height (+18%, P < 0.05) compared with wild-type (WT) mice. In contrast, the longitudinal bone growth ceased in old ERαAF-10 mice (tibia: −4.9%, P < 0.01). Importantly, the proximal tibial growth plates were closed in all old ERαAF-10 mice while they were open in all WT mice. Growth plate closure was associated with a significantly altered balance between chondrocyte proliferation and apoptosis in the growth plate. In conclusion, old female ERα−/− mice display a prolonged and enhanced longitudinal bone growth associated with increased growth plate height, resembling the growth phenotype of patients with inactivating mutations in ERα or aromatase. In contrast, ERαAF-1 deletion results in a hyperactive ERα, altering the chondrocyte proliferation/apoptosis balance, leading to growth plate closure. This suggests that growth plate closure is induced by functions of ERα that do not require AF-1 and that ERαAF-1 opposes growth plate closure.

EFFECT OF WITHDRAWAL OF GROWTH HORMONE ADMINISTRATION ON LONGITUDINAL BONE GROWTH IN THE HYPOPHYSECTOMIZED RAT

1974 ◽  
Vol 75 (1) ◽  
pp. 11-23 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson
Keyword(s):  
Growth Hormone ◽  
Growth Plate ◽  
Bone Growth ◽  
Proximal Tibia ◽  
Bovine Growth Hormone ◽  
Sprague Dawley ◽  
Cell Production ◽  
Longitudinal Bone Growth ◽  
Hormone Administration ◽  
Sprague Dawley Rats

ABSTRACT Bovine growth hormone was given daily for 10 days to female Sprague-Dawley rats hypophysectomized at the age of 60 days, beginning 15 days post-operatively. Longitudinal bone growth, studied in the proximal tibia, was reactivated and continued at an accelerating rate during the period of hormone administration and for a further 5 days after its withdrawal, but then ceased. The effect of withdrawal of growth hormone on the width of the growth plate of proximal tibia, the size of its degenerative cells, and the weight of body and heart was also studied. The cell production in the proximal growth plate of tibia was calculated. The changes in longitudinal bone growth were found to be due mainly to changes in cell production in the growth plate.

EFFECT OF DOSE AND ADMINISTRATION PERIOD OF GROWTH HORMONE ON LONGITUDINAL BONE GROWTH IN THE HYPOPHYSECTOMIZED RAT

1973 ◽  
Vol 74 (1) ◽  
pp. 1-23 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson ◽  
K. Menander-Sellman ◽  
A. Stenström
Keyword(s):  
Growth Hormone ◽  
Growth Plate ◽  
Dose Response ◽  
Bone Growth ◽  
Growth Parameters ◽  
Growth Stimulation ◽  
The Body ◽  
Sprague Dawley ◽  
Longitudinal Bone Growth ◽  
Response Determination

ABSTRACT The effect of bovine growth hormone (NIH-GH-B15) on the growth in length of the proximal growth plate of the tibia in hypophysectomized female Sprague-Dawley rats was studied by the tetracycline method. The width of the growth plate was also determined and the weight of the body and heart was registered. The completeness of the hypophysectomy was determined microscopically. The daily sc injection of 25 μg NIH-GH-B15 for 10, 20 or 30 days resulted in an increasing growth in length with increasing administration period. When various doses (5, 25, 100 or 400 μg) NIH-GH-B15 were administered daily for 20 days, the growth in length increased with the dose. A single injection of 45 mg/kg cortisone acetate given at hypophysectomy depressed the growth stimulation of growth hormone. The age at hypophysectomy also influenced the growth hormone-induced growth stimulation. Animals hypophysectomized at 40 days of age had a higher growth in length for the same doses and administration periods of growth hormone than those operated at 60 days of age. The width of the growth plate of the proximal tibia and the weight of the body and heart responded in a similar manner as the longitudinal bone growth to various doses and administration periods of growth hormone, but the changes were less obvious. The dose-response relation after the administration of various doses of growth hormone for 20 days was tested for different growth parameters by the index of precision (λ). Of the growth parameters in this investigation, the accumulated growth in length in animals hypophysectomized at 60 days of age without cortisone at operation was found to be most suitable for dose-response determination of growth hormone. The intention is to develop a bio-assay for growth hormone.

scholarly journals Indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway

2019 ◽  
Vol 51 (9) ◽  
pp. 1-10
Author(s):  
Sehee Choi ◽  
Pu-Hyeon Cha ◽  
Hyun-Yi Kim ◽  
Kang-Yell Choi
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Ex Vivo ◽  
Hormone Treatment ◽  
Current Approach ◽  
Plate Height ◽  
Growth Plate Chondrocytes ◽  
Longitudinal Bone Growth ◽  
Chondrocyte Maturation

Abstract Researchers have shown increased interest in determining what stimulates height. Currently, many children undergo precocious puberty, resulting in short stature due to premature closure of the growth plate. However, the current approach for height enhancement is limited to growth hormone treatment, which often results in side effects and clinical failure and is costly. Although recent studies have indicated the importance of paracrine signals in the growth plate for longitudinal bone growth, height-stimulating agents targeting the signaling pathways involved in growth plate maturation remain unavailable in the clinic. The Wnt/β-catenin pathway plays a major role in the maturation of growth plate chondrocytes. In this study, by using an ex vivo tibial culture system, we identified indirubin-3′-oxime (I3O) as a compound capable of enhancing longitudinal bone growth. I3O promoted chondrocyte proliferation and differentiation via activation of the Wnt/β-catenin pathway in vitro. Intraperitoneal injection of I3O in adolescent mice increased growth plate height along with incremental chondrocyte maturation. I3O promoted tibial growth without significant adverse effects on bone thickness and articular cartilage. Therefore, I3O could be a potential therapeutic agent for increasing height in children with growth retardation.

EFFECT OF THYROXINE AND GROWTH HORMONE ON LONGITUDINAL BONE GROWTH IN THE HYPOPHYSECTOMIZED RAT

1973 ◽  
Vol 74 (1) ◽  
pp. 24-40 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson
Keyword(s):  
Growth Hormone ◽  
Growth Plate ◽  
Bone Growth ◽  
The Body ◽  
Heart Weight ◽  
Optimum Dose ◽  
Sprague Dawley ◽  
Promoting Effect ◽  
Longitudinal Bone Growth ◽  
Stimulation Of

ABSTRACT The effect of L-thyroxine and bovine growth hormone (NIH-GH-B16) on the growth in length from the proximal growth plate of the tibia in hypophysectomized female Sprague-Dawley rats was studied by the tetracycline method. The width of the growth plate was also determined, and the weight of the body and heart was registered. Completeness of the hypophysectomy was determined microscopically. Daily sc injections of 5, 10, 20 or 40 μg/kg L-thyroxine alone, or in combination with 25 or 100 μg NIH-GH-B16, were given for 20 days, starting 15 days after hypophysectomy which was performed when the rats were 60 days of age. Thyroxine alone resulted in stimulation of the longitudinal bone growth with an optimum effect at 10–20 μg/kg. Further increase of the thyroxine dose did not increase the bone growth. Thyroxine given in association with growth hormone had a higher growing promoting effect than thyroxine or growth hormone alone. The growth stimulation of the two hormones was also significantly higher than the expected additive effect, indicating a potentiating synergism. When thyroxine and growth hormone were given in combination, the longitudinal bone growth reached an optimum for almost the same dose (20 μg/kg) of thyroxine as when it was given alone. At this optimum dose of thyroxine, the dose of growth hormone determined the longitudinal bone growth. The width of the growth plate was not influenced by thyroxine administration. The body weight decreased somewhat when thyroxine was given alone, and the combination with growth hormone seemed to compensate for this weight loss. The heart weight was found to increase with increasing doses of thyroxine both when given alone and in association with growth hormone.

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