scholarly journals Hormonal Aspects of the Muscle-Bone Unit

2008 ◽  
pp. S159-S169
Author(s):  
I Žofková
Keyword(s):  
Bone Formation ◽  
Muscle Mass ◽  
Mechanical Load ◽  
Osteoporotic Fractures ◽  
Functional System ◽  
Adult Men ◽  
Sexual Steroids ◽  
Common Control ◽  
Igf I ◽  
Functional Complex

Osteoporotic fractures are the result of low density and especially inferior bone quality (microarchitecture) caused by both internal (genes, hormones) and external (life style) influences. Bone mechanosensors are extremely important for the overall integrity of the skeleton, because in response to mechanical load they activate its modeling, resulting in an increase in bone density and strength. The largest physiological loads are caused by muscle contractions. Bone mass in adult men has a closer relationship to muscle mass than is case in women. The sexual differences in the relationship between bone and muscle mass are also apparent in children. Based on the mechanostatic theory, the muscle-bone unit has been defined as a functional system whose components are under the common control of the hormones of the somatotropin-IGF-I axis, sexual steroids, certain adipose tissue hormones and vitamin D. The osteogenic effects of somatotropin-IGF-I system are based on the stimulation of bone formation, as well as increase in muscle mass. Moreover, somatotropin decreases the bone mechanostat threshold and reinforces the effect of physical stress on bone formation. The system, via the muscle-bone unit, plays a significant role in the development of the childhood skeleton as well as in its stability during adulthood. The muscle and bone are also the targets of androgens, which increase bone formation and the growth of muscle mass in men and women, independently of IGF-I. The role of further above-mentioned hormones in regulation of this unified functional complex is also discussed.

Milk Basic Protein Promotes Bone Formation and Suppresses Bone Resorption in Healthy Adult Men

2001 ◽  
Vol 65 (6) ◽  
pp. 1353-1357 ◽  
Author(s):  
Yasuhiro TOBA ◽  
Yukihiro TAKADA ◽  
Yasuhiro MATSUOKA ◽  
Yoshikazu MORITA ◽  
Mutsumi MOTOURI ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Basic Protein ◽  
Healthy Adult ◽  
Adult Men ◽  
Milk Basic Protein

scholarly journals Mechanical Load Increases in Bone Formation via a Sclerostin-Independent Pathway

2014 ◽  
Vol 29 (11) ◽  
pp. 2456-2467 ◽  
Author(s):  
Alyson Morse ◽  
Michelle Maree McDonald ◽  
Natalie H Kelly ◽  
Katherine M Melville ◽  
Aaron Schindeler ◽  
...  
Keyword(s):  
Bone Formation ◽  
Mechanical Load

scholarly journals Effect of mechanical loading on insulin-like growth factor-I gene expression in rat tibia

2007 ◽  
Vol 192 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Christianne M A Reijnders ◽  
Nathalie Bravenboer ◽  
Annechien M Tromp ◽  
Marinus A Blankenstein ◽  
Paul Lips
Keyword(s):  
Bone Formation ◽  
Mrna Expression ◽  
Mechanical Loading ◽  
Mechanical Stimulation ◽  
Molecular Mechanisms ◽  
Bone Marrow Cells ◽  
Mechanical Stimuli ◽  
Igf I ◽  
Female Wistar Rats ◽  
Tibia Shaft

Mechanical loading plays an essential role in maintaining skeletal integrity. Mechanical stimulation leads to increased bone formation. However, the cellular and molecular mechanisms that are involved in the translation of mechanical stimuli into bone formation, are not completely understood. Growth factors and osteocytes, which act as mechanosensors, play a key role during the bone formation after mechanical stimulation. The aim of this study was to characterize the role of IGF-I in the translation of mechanical stimuli into bone formation locally in rat tibiae. Fifteen female Wistar rats were randomly assigned to three groups (n = 5): load, sham-loaded, and control. The four-point bending model of Forwood and Turner was used to induce a single period of mechanical loading on the tibia shaft. The effects of mechanical loading on IGF-I mRNA expression were determined with non-radioactive in situ hybridization on decalcified tibiae sections, 6 h after the loading session. Endogenous IGF-I mRNA was expressed in trabecular and cortical osteoblasts, some trabecular and sub-endocortical osteocytes, intracortical endothelial cells of blood vessels, and periosteum. Megakaryocytes, macrophages, and myeloid cells also expressed IGF-I mRNA. In the growth plate, IGF-I mRNA was located in proliferative and hypertrophic chondrocytes. Mechanical loading did not affect the IGF-I mRNA expression in osteoblasts, bone marrow cells, and chondrocytes, but the osteocytes at the endosteal side of the shaft showed a twofold increase of IGF-I mRNA expression. The proportion of IGF-I mRNA positive osteocytes in loaded tibiae was 29.3 ± 12.9% (mean ± s.d.; n = 5), whereas sham-loaded and contra-lateral control tibiae exhibited 16.7 ± 4.4% (n = 5) and 14.7 ± 4.2% (n = 10) respectively (P < 0.05). Lamellar bone formation after a single mechanical loading session was observed at the endosteal side of the shaft. In conclusion, a single loading session results in a twofold up-regulation of IGF-I mRNA synthesis in osteocytes which are present in multiple layers extending into the cortical bone of mechanically stimulated tibia shaft 6 h after loading. This supports the hypothesis that IGF-I, which is located in osteocytes, is involved in the translation of mechanical stimuli into bone formation.

scholarly journals IGF-I, insulin and prostate cancer

2009 ◽  
Vol 53 (8) ◽  
pp. 969-975 ◽  
Author(s):  
Giovanna A. Balarini Lima ◽  
Lívia L. Corrêa ◽  
Rafael Gabrich ◽  
Luiz Carlos D. de Miranda ◽  
Mônica R. Gadelha
Keyword(s):  
Prostate Cancer ◽  
Growth Factors ◽  
Cancer Risk ◽  
Cancer Cells ◽  
Growth Regulation ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Adult Men ◽  
Igf I ◽  
High Insulin

Prostate cancer is the second most frequent malignancy diagnosed in adult men. Androgens are considered the primary growth factors for prostate normal and cancer cells. However, other non-androgenic growth factors are involved in the growth regulation of prostate cancer cells. The association between IGF-I and prostate cancer risk is well established. However, there is no evidence that the measurement of IGF-I enhances the specificity of prostate cancer detection beyond that achievable by serum prostate-specific antigen (PSA) levels. Until now, there is no consensus on the possible association between IGFBP-3 and prostate cancer risk. Although not well established, it seems that high insulin levels are particularly associated with risk of aggressive prostatic tumours. This review describes the physiopathological basis, epidemiological evidence, and animal models that support the association of the IGFs family and insulin with prostate cancer. It also describes the potential therapies targeting these growth factors that, in the future, can be used to treat patients with prostate cancer.

scholarly journals Dietary acid–base load and its association with risk of osteoporotic fractures and low estimated skeletal muscle mass

2020 ◽  
Vol 74 (S1) ◽  
pp. 33-42
Author(s):  
Richard P. G. Hayhoe ◽  
Asmaa Abdelhamid ◽  
Robert N. Luben ◽  
Kay-Tee Khaw ◽  
Ailsa A. Welch
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Osteoporotic Fractures ◽  
Acid Base ◽  
Dietary Acid ◽  
Base Load

Romosozumab: A first-in-class sclerostin inhibitor for osteoporosis

2020 ◽  
Vol 77 (23) ◽  
pp. 1949-1956
Author(s):  
Caitlin Prather ◽  
Erin Adams ◽  
Whitney Zentgraf
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Bone Resorption ◽  
Bone Formation ◽  
English Language ◽  
Safety Concern ◽  
Osteoporotic Fractures ◽  
Mineral Density ◽  
Treatment Of Osteoporosis ◽  
Poster Presentations

Abstract Purpose The purpose of this article is to review the pharmacology, efficacy, and safety of the sclerostin inhibitor romosozumab for the treatment of osteoporosis, including data from clinical trials of the drug. Summary A review of the literature was performed by searching PubMed and MEDLINE for all relevant articles published between January 2014 and February 2020 using the keywords romosozumab, romosozumab-aqqg, osteoporosis, and fracture. All relevant English-language articles evaluating the pharmacology, efficacy, or safety of romosozumab for the treatment of osteoporosis in humans were included; poster presentations were excluded. Romosozumab has been approved by the Food and Drug Administration and is considered both safe and effective for the treatment of osteoporosis in high-risk postmenopausal females. Phase 2 and phase 3 clinical trials have shown a statistically significant decrease in new vertebral fractures and an increase in bone mineral density with romosozumab use, as compared with both placebo use and use of alternative osteoporosis therapies. The primary safety concern is a potential risk of cardiovascular events; additionally, hypocalcemia must be corrected prior to initiation. Romosozumab is the first anabolic medication that both increases bone formation and decreases bone resorption. Data suggest that romosozumab is more effective than oral bisphosphonates in preventing osteoporotic fractures, though cost and safety concerns must be considered. Conclusion Romosozumab is a novel, 12-month treatment option for postmenopausal women at high risk for osteoporotic fracture that both increases bone formation and decreases bone resorption.

scholarly journals Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naoki Kuramoto ◽  
Kazuhiro Nomura ◽  
Daisuke Kohno ◽  
Tadahiro Kitamura ◽  
Gerard Karsenty ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Hypertrophy ◽  
Mechanical Load ◽  
Static Condition ◽  
Ribosomal Protein S6 ◽  
Pi3k Signaling Pathway ◽  
Induced Changes

AbstractPhosphatidylinositol 3-kinase (PI3K) plays an important role in protein metabolism and cell growth. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3′-phosphoinositide–dependent kinase 1 (PDK1), a key component of PI3K signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of mechanical load–induced muscle hypertrophy. Whereas mechanical load-induced changes in gene expression were not affected, the phosphorylation of ribosomal protein S6 kinase (S6K) and S6 induced by mechanical load was attenuated in skeletal muscle of M-PDK1KO mice, suggesting that PDK1 regulates muscle hypertrophy not through changes in gene expression but through stimulation of kinase cascades such as the S6K-S6 axis, which plays a key role in protein synthesis. Administration of the β2-adrenergic receptor (AR) agonist clenbuterol activated the S6K-S6 axis in skeletal muscle and induced muscle hypertrophy in mice. These effects of clenbuterol were attenuated in M-PDK1KO mice, and mechanical load–induced activation of the S6K-S6 axis and muscle hypertrophy were inhibited in mice with skeletal muscle–specific deficiency of β2-AR. Our results suggest that PDK1 regulates skeletal muscle mass under the static condition and that it contributes to mechanical load–induced muscle hypertrophy, at least in part by mediating signaling from β2-AR.

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