Peptides from Euphausia superba Promote Longitudinal Bone Growth by Accelerating Growth Plate Chondrocyte Proliferation and Hypertrophy

2020 ◽  
Vol 21 ◽  
Author(s):  
Yufeng Dai ◽  
Zhuo Li ◽  
Meng Fu ◽  
Yanqi Li ◽  
Changhu Xue ◽  
...  
Keyword(s):  
Short Stature ◽  
Growth Plate ◽  
Bone Growth ◽  
Euphausia Superba ◽  
Nutritional Intervention ◽  
Bone Morphogenetic Protein 2 ◽  
Mice Model ◽  
Serum Growth Hormone ◽  
Longitudinal Bone Growth ◽  
Related Transcription Factor

Background: With the improvements in living standards, height is getting more attention. Malnutrition is one of the main causes of children's short stature, therefore nutritional intervention in adolescence is the key to prevent short stature. The peptides from Antarctic krill (AKPs), the ideal protein model, act in bone formation and anti-osteoporosis. However, the studies on promoting longitudinal bone growth by AKPs have not been reported. Methods: Three-week-old male ICR mice, to construct the adolescent mice model, randomly divided into three groups: normal group, casein group (casein, 300 mg/kgꞏBW), and AKPs group (AKPs, 300 mg/kgꞏBW). After 21 days of drugs administration, the effects of AKPs on serum biochemical indexes and femur histomorphology of mice, and the mechanism of AKPs promoting longitudinal bone growth was discussed. Results: AKPs significantly increased the longitudinal bone growth and improved bone strength. In addition, AKPs remarkably promoted proliferation and hypertrophy of chondrocytes in the growth plate. The further mechanism revealed that AKPs increased serum growth hormone (GH) and insulin-like growth factors-1(IGF-1) contents, which activated the downstream GH/IGF-1 axis signaling pathways. Moreover, AKPs induced the secretion and expression of bone morphogenetic protein 2 (BMP-2) and triggered the activation of BMP2-dependent Smads signaling. AKPs also activated Wnt/βcatenin signaling, and synergistically activated the expression of runt-related transcription factor 2 (Runx 2) and osterix (OSX). Conclusion: AKPs promoted longitudinal bone growth by activating GH/IGF-1 axis, BMP-2/Smads and Wnt/β-catenin pathways, suggesting AKPs to be a potential nutrient fortifier for longitudinal bone growth.

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.

Fluoride Inhibits Longitudinal Bone Growth by Acting Directly at the Growth Plate in Cultured Neonatal Rat Metatarsal Bones

2019 ◽  
Vol 197 (2) ◽  
pp. 522-532 ◽  
Author(s):  
Rui Ma ◽  
Shuang Liu ◽  
Tingting Qiao ◽  
Demin Li ◽  
Ruixue Zhang ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Neonatal Rat ◽  
Longitudinal Bone Growth ◽  
Metatarsal Bones

scholarly journals Nuclear Factor-κB p65 Facilitates Longitudinal Bone Growth by Inducing Growth Plate Chondrocyte Proliferation and Differentiation and by Preventing Apoptosis

2007 ◽  
Vol 282 (46) ◽  
pp. 33698-33706 ◽  
Author(s):  
Shufang Wu ◽  
Janna K. Flint ◽  
Geoffrey Rezvani ◽  
Francesco De Luca
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Chondrocyte Apoptosis ◽  
Pyrrolidine Dithiocarbamate ◽  
Growth Plate Chondrocytes ◽  
Chondrocyte Proliferation ◽  
Longitudinal Bone Growth ◽  
Metatarsal Bones ◽  
Proliferation And Differentiation ◽  
Cultured Chondrocytes

NF-κB is a group of transcription factors involved in cell proliferation, differentiation, and apoptosis. Mice deficient in the NF-κB subunits p50 and p52 have retarded growth, suggesting that NF-κB is involved in bone growth. Yet, it is not clear whether the reduced bone growth of these mice depends on the lack of NF-κB activity in growth plate chondrocytes. Using cultured rat metatarsal bones and isolated growth plate chondrocytes, we studied the effects of two NF-κB inhibitors (pyrrolidine dithiocarbamate (PDTC) or BAY11-7082 (BAY)), p65 short interference RNA (siRNA), and of the overexpression of p65 on chondrocyte proliferation, differentiation, and apoptosis. To further define the underlying mechanisms, we studied the functional interaction between NF-κB p65 and BMP-2 in chondrocytes. PDTC and BAY suppressed metatarsal linear growth. Such growth inhibition resulted from decreased chondrocyte proliferation and differentiation and from increased chondrocyte apoptosis. In cultured chondrocytes, the inhibition of NF-κB p65 activation (by PDTC and BAY) and expression (by p65 siRNA) led to the same findings observed in cultured metatarsal bones. In contrast, overexpression of p65 in cultured chondrocytes induced chondrocyte proliferation and differentiation and prevented apoptosis. Although PDTC, BAY, and p65 siRNA reduced the expression of BMP-2 in cultured growth plate chondrocytes, the overexpression of p65 increased it. The addition of Noggin, a BMP-2 antagonist, neutralized the stimulatory effects of p65 on chondrocyte proliferation and differentiation, as well as its anti-apoptotic effect. In conclusion, our findings indicate that NF-κB p65 expressed in growth plate chondrocytes facilitates growth plate chondrogenesis and longitudinal bone growth by inducing BMP-2 expression and activity.

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.

Part 2. Review and meta‐analysis of studies on modulation of longitudinal bone growth and growth plate activity: A micro‐scale perspective

2021 ◽  
Author(s):  
Christian R. D'Andrea ◽  
Ausilah Alfraihat ◽  
Anita Singh ◽  
Jason B. Anari ◽  
Patrick J. Cahill ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Meta Analysis ◽  
Longitudinal Bone Growth ◽  
Micro Scale

scholarly journals The Role of the Growth Plate in Longitudinal Bone Growth

1991 ◽  
Vol 70 (8) ◽  
pp. 1806-1814 ◽  
Author(s):  
M. PINES ◽  
S. HURWITZ
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Longitudinal Bone Growth
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