scholarly journals Effects of Eleutherococcus Extract Mixture on Endochondral Bone Formation in Rats

2019 ◽  
Vol 20 (5) ◽  
pp. 1253 ◽  
Author(s):  
Donghun Lee ◽  
Sung Lee ◽  
Namhoon Cho ◽  
Young-Sik Kim ◽  
Jungbin Song ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Formation ◽  
Female Adolescent ◽  
Bone Morphogenetic Protein 2 ◽  
Endochondral Bone Formation ◽  
Insulin Like Growth Factor ◽  
Endochondral Bone ◽  
Fluorescent Band ◽  
Traditional Medicines

Eleutherococcus extract mixture (EEM) is an herbal mixture of dried stem of Eleutherococcus sessiliflorus and germinated barley, which has been highly effective, in previous screening and among the traditional medicines to tonify innate qi and acquired qi, respectively. In this study, we investigate the effects of EEM on endochondral bone formation. Female adolescent rats were given EEM, growth hormone or vehicle for 10 days. Tetracycline was intraperitoneally injected to light the fluorescent band 72 h before sacrifice to determine endochondral bone formation. In order to evaluate endocrine or paracrine/autocrine mechanisms, expressions of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), or bone morphogenetic protein 2 (BMP2) were evaluated after EEM administration in liver or growth plate (GP). EEM oral administration significantly increased endochondral bone formation and proliferative and hypertrophic zonal heights of tibial GP. EEM also upregulated hepatic IGF1 and IGFBP3 mRNA expressions, and IGF1 and BMP2 expressions in GP. Taken together, EEM increases endochondral bone formation through stimulating proliferation and hypertrophy with upregulation of hepatic IGF1 and IGFBP3 expressions. Considering immunohistochemical studies, the effect of EEM may be due to increased local IGF1 and BMP2 expression in GP, which may be considered growth hormone (GH)-dependent endocrine and autocrine/paracrine pathways.

scholarly journals Effects of Short-Term Insulin-Like Growth Factor-I (IGF-I) or Growth Hormone (GH) Treatment on Bone Metabolism and on Production of 1,25-Dihydroxycholecalciferol in GH-Deficient Adults1

1998 ◽  
Vol 83 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Tarcisio Bianda ◽  
Yvonne Glatz ◽  
Roger Bouillon ◽  
Ernst Rudolf Froesch ◽  
Christoph Schmid
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Formation ◽  
Bone Turnover ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Administration of insulin-like growth factor-I (IGF-I) or growth hormone (GH) is known to stimulate bone turnover and kidney function. To investigate the effects of IGF-I and GH on markers of bone turnover, eight adult GH-deficient patients (48 ± 14 yr of age) were treated with IGF-I (5 μg/kg/h in a continuous sc infusion) and GH (0.03 IU/kg/daily sc injection at 2000 h) in a randomized cross-over study. We monitored baseline values for three consecutive days before initiating the five-day treatment period, as well as the wash-out period of ten weeks. Serum osteocalcin, carboxyterminal and aminoterminal propeptide of type I procollagen (PICP and PINP, respectively) increased significantly within 2–3 days of both treatments (P < 0.02) and returned to baseline levels within one week after the treatment end. The changes in resorption markers were less marked as compared with formation markers. Total 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) rose significantly, whereas PTH and calcium levels remained unchanged during either treatment. Conclusions: Because the rapid increase in markers of bone formation was not preceded by an increase in resorption markers, IGF-I is likely to stimulate bone formation by a direct effect on osteoblasts. Moreover, because PTH, calcium, and phosphate remained unchanged, IGF-I appears to stimulate renal 1α-hydroxylase activity in vivo.

scholarly journals Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth Rate

Marine Drugs ◽  
2020 ◽  
Vol 18 (9) ◽  
pp. 472
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Jayasingha Arachchige Chathuranga Chanaka Jayasingha ◽  
Yung Hyun Choi ◽  
Eui Kyun Park ◽  
You-Jin Jeon ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Rate ◽  
Growth Factor ◽  
Bone Formation ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Calcium Deposition ◽  
Insulin Like Growth Factor ◽  
Zebrafish Larvae ◽  
Gsk 3Β

Fermented oyster (Crassostrea gigas) extract (FO) prevents ovariectomy-induced osteoporosis by inhibiting osteoclastogenesis and activating osteogenesis. However, the molecular mechanisms underlying FO-mediated bone formation and growth rate are unclear. In the current study, we found that FO significantly upregulated the expression of growth-promoting genes in zebrafish larvae including insulin-like growth factor 1 (zigf-1), insulin-like growth factor binding protein 3 (zigfbp-3), growth hormone-1 (zgh-1), growth hormone receptor-1 (zghr-1), growth hormone receptor alpha (zghra), glucokinase (zgck), and cholecystokinin (zccka). In addition, zebrafish larvae treated with 100 μg/mL FO increased in total body length (3.89 ± 0.13 mm) at 12 days post fertilization (dpf) compared to untreated larvae (3.69 ± 0.02 mm); this effect was comparable to that of the β-glycerophosphate-treated zebrafish larvae (4.00 ± 0.02 mm). Furthermore, FO time- and dose-dependently increased the extracellular release of IGF-1 from preosteoblast MC3T3-E1 cells, which was accompanied by high expression of IGF-1. Pharmacological inhibition of IGF-1 receptor (IGF-1R) using picropodophyllin (PPP) significantly reduced FO-mediated vertebrae formation (from 9.19 ± 0.31 to 5.53 ± 0.35) and growth performance (from 3.91 ± 0.02 to 3.69 ± 0.01 mm) in zebrafish larvae at 9 dpf. Similarly, PPP significantly decreased FO-induced calcium deposition in MC3T3-E1 cells by inhibiting GSK-3β phosphorylation at Ser9. Additionally, DOI hydrochloride, a potent stabilizer of GSK-3β, reduced FO-induced nuclear translocation of RUNX2. Transient knockdown of IGF-1Rα/β using specific silencing RNA also resulted in a significant decrease in calcium deposition and reduction in GSK-3β phosphorylation at Ser9 in MC3T3-E1 cells. Altogether, these results indicate that FO increased phosphorylated GSK-3β at Ser9 by activating the autocrine IGF-1-mediated IGF-1R signaling pathway, thereby promoting osteogenesis and growth performance. Therefore, FO is a potential nutritional supplement for bone formation and growth.

scholarly journals A Transgenic Rat for Noninvasive Assessment of Chondrogenesis in Vivo

Cartilage ◽  
2021 ◽  
pp. 194760352110572
Author(s):  
Elisabeth Ferreira ◽  
Landon B. Gatrell ◽  
Luke Childress ◽  
Hong Wu ◽  
Ryan M. Porter
Keyword(s):  
Bone Formation ◽  
Heterotopic Ossification ◽  
Ex Vivo ◽  
Firefly Luciferase ◽  
Bone Morphogenetic Protein 2 ◽  
Endochondral Bone Formation ◽  
Transgenic Rat ◽  
Regulatory Sequences ◽  
Endochondral Bone

Objective To support the preclinical evaluation of therapeutics that target chondrogenesis, our goal was to generate a rat strain that can noninvasively report endogenous chondrogenic activity. Design A transgene was constructed in which the dual expression of bioluminescent (firefly luciferase) and fluorescent (mCherry) reporters is controlled by regulatory sequences from rat Col2a1. Candidate lines were established on a Lewis background and characterized by serial bioluminescence imaging as well as ex vivo measurement of molecular reporter levels in several tissues. The sensitivity and specificity of the reporter strain were assessed in models of orthotopic and ectopic chondrogenesis. Results Substantial bioluminescence signal was detected from cartilaginous regions, including the appendicular synovial joints, spine, sternum, nose, and pinnae. Bioluminescent radiance was intense at 1 month of age, rapidly declined with continued development, yet remained detectable in 2-year-old animals. Explant imaging and immunohistochemistry confirmed that both molecular reporters were localized to cartilage. Implantation of wild-type bone marrow stromal cells into osteochondral defects made in both young adult and aged reporter rats led to a time-dependent elevation of intra-articular reporter activity concurrent with cartilaginous tissue repair. To stimulate ectopic, endochondral bone formation, bone morphogenetic protein 2 was overexpressed in the gastrocnemius muscle, which led to bioluminescent signal that closely preceded heterotopic ossification. Conclusions This strain can help develop strategies to stimulate cartilage repair and endochondral bone formation or to inhibit chondrogenesis associated with heterotopic ossification.

scholarly journals ADAMTS-7, a Direct Target of PTHrP, Adversely Regulates Endochondral Bone Growth by Associating with and Inactivating GEP Growth Factor

2009 ◽  
Vol 29 (15) ◽  
pp. 4201-4219 ◽  
Author(s):  
Xiao-Hui Bai ◽  
Da-Wei Wang ◽  
Li Kong ◽  
Yan Zhang ◽  
Yi Luan ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Bone Formation ◽  
Proteolytic Activity ◽  
Bone Growth ◽  
Endochondral Bone Formation ◽  
Chondrocyte Differentiation ◽  
Growth Plate Chondrocytes ◽  
Endochondral Bone ◽  
Direct Target

ABSTRACT ADAMTS-7, a metalloproteinase that belongs to ADAMTS family, is important for the degradation of cartilage extracellular matrix proteins in arthritis. Herein we report that ADAMTS-7 is upregulated during chondrocyte differentiation and demonstrates the temporal and spatial expression pattern during skeletal development. ADAMTS-7 potently inhibits chondrocyte differentiation and endochondral bone formation, and this inhibition depends on its proteolytic activity. The cysteine-rich domain of ADAMTS-7 is required for its interaction with the extracellular matrix, and the C-terminal four-thrombospondin motifs are necessary for its full proteolytic activity and inhibition of chondrocyte differentiation. ADAMTS-7 is an important target of canonical PTHrP signaling, since (i) PTHrP induces ADAMTS-7, (ii) ADAMTS-7 is downregulated in PTHrP null mutant (PTHrP−/−) growth plate chondrocytes, and (iii) blockage of ADAMTS-7 almost abolishes PTHrP-mediated inhibition of chondrocyte hypertrophy and endochondral bone growth. ADAMTS-7 associates with granulin-epithelin precursor (GEP), an autocrine growth factor that has been implicated in tissue regeneration, tumorigenesis, and inflammation. In addition, ADAMTS-7 acts as a new GEP convertase and neutralizes GEP-stimulated endochondral bone formation. Collectively, these findings demonstrate that ADAMTS-7, a direct target of PTHrP signaling, negatively regulates endochondral bone formation by associating with and inactivating GEP chondrogenic growth factor.

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