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Frontiers in Endocrinology 2023Bone and skeletal muscle work in coordination to maintain the function of the musculoskeletal system, in which skeletal muscle contraction drives the movement of the... (Review)
Review
Bone and skeletal muscle work in coordination to maintain the function of the musculoskeletal system, in which skeletal muscle contraction drives the movement of the bone lever system while bone provides insert sites for skeletal muscle through the bone-muscle junction. Existing evidence suggests that factors secreted by skeletal muscle and bone mediate the interaction between the two tissues. Herein, we focused on the relationship between skeletal muscle and bone and the underlying mechanism of the interaction. Exercise can promote bone strength and secrete osteocalcin and insulin-like growth factor I into the blood, thus improving muscle quality. In addition, exercise can also promote myostatin, interleukin-6, Irisin, and apelin in muscles to enter the blood so that they can act on bones to maintain the balance between bone absorption and bone formation. There is a special regulatory axis interleukin-6/osteocalcin between myokines and osteokines, which is mainly influenced by exercise. Therefore, we pay attention to the important factors in the bone-muscle intersection that are affected by exercise, which were found or their functions were expanded, which strengthened the connection between organs of the whole body, highlighting the importance of exercise and contributing to the diagnosis, prevention, and treatment of osteoporosis and sarcopenia in the clinic.
Topics: Bone and Bones; Exercise; Interleukin-6; Muscle, Skeletal; Osteocalcin
PubMed: 38239981
DOI: 10.3389/fendo.2023.1287972 -
Calcified Tissue International Feb 2023Vitamin K, a cofactor for the γ-glutamyl carboxylase enzyme, is required for the post-translational activation of osteocalcin and matrix Gla protein, which play a key... (Review)
Review
Vitamin K, a cofactor for the γ-glutamyl carboxylase enzyme, is required for the post-translational activation of osteocalcin and matrix Gla protein, which play a key role in bone and muscle homeostasis. In vivo and in vitro models for osteoporosis and sarcopenia suggest the vitamin K could exert a positive effect in both conditions. In bone, it increases osteoblastogenesis, whilst decreases osteoclast formation and function. In muscle, it is associated with increased satellite cell proliferation and migration and might play a role in energy metabolism. Observational trials suggest that high levels of vitamin K are associated with increased bone mineral density and reduced fracture risk. However, interventional studies for vitamin K supplementation yielded conflicting results. Clinical trials in sarcopenia suggest that vitamin K supplementation could improve muscle mass and function. One of the main limitations on the vitamin K studies are the technical challenges to measure its levels in serum. Thus, they are obtained from indirect sources like food questionnaires, or levels of undercarboxylated proteins, which can be affected by other environmental or biological processes. Although current research appoints to a beneficial effect of vitamin K in bone and muscle, further studies overcoming the current limitations are required in order to incorporate this supplementation in the clinical management of patients with osteosarcopenia.
Topics: Humans; Vitamin K; Bone Density; Sarcopenia; Bone and Bones; Osteocalcin; Muscles
PubMed: 35150288
DOI: 10.1007/s00223-022-00955-3 -
ELife Jan 2021Osteocalcin is a bone matrix protein that acts like a hormone when it reaches the blood, and has different effects in mice and humans.
Osteocalcin is a bone matrix protein that acts like a hormone when it reaches the blood, and has different effects in mice and humans.
Topics: Animals; Glycosylation; Hormones; Mice; Osteocalcin
PubMed: 33480844
DOI: 10.7554/eLife.65719 -
International Journal of Molecular... Aug 2021Vitamin K and Vitamin K-dependent proteins (VKDPs) are best known for their pivotal role in blood coagulation. Of the 14 VKPDs identified in humans to date, 6 play also... (Review)
Review
Vitamin K and Vitamin K-dependent proteins (VKDPs) are best known for their pivotal role in blood coagulation. Of the 14 VKPDs identified in humans to date, 6 play also important roles in skeletal biology and disease. Thus, osteocalcin, also termed bone Gla-protein, is the most abundant non-collagenous protein in bone. Matrix Gla protein and Ucma/GRP on the other hand are highly abundant in cartilage. Furthermore, periostin, protein S, and growth arrest specific 6 protein (GAS 6) are expressed in skeletal tissues. The roles for these VKDPs are diverse but include the control of calcification and turnover of bone and cartilage. Vitamin K plays an important role in osteoporosis and serum osteocalcin levels are recognized as a promising marker for osteoporosis. On the other hand, matrix Gla protein and Ucma/GRP are associated with osteoarthritis. This review focuses on the roles of these three VKDPs, osteocalcin, matrix Gla protein and Ucma/GRP, in skeletal development and disease but will also summarize the roles the other skeletal VKDPs (periostin, protein S and GAS6) in skeletal biology.
Topics: Animals; Bone Development; Humans; Osteocalcin; Osteoporosis; Vitamin K
PubMed: 34502245
DOI: 10.3390/ijms22179328 -
Current Diabetes Reports Dec 2014There are well-established associations between diabetes and fracture risk and yet the mechanism underlying these associations are controversial. Guided by a series of... (Review)
Review
There are well-established associations between diabetes and fracture risk and yet the mechanism underlying these associations are controversial. Guided by a series of mouse studies, a specific form of the bone protein, osteocalcin, was proposed to be the mechanistic link between these two chronic diseases. Translation to humans initially appeared elusive in part because serum concentrations of osteocalcin are a biomarker of bone turnover and not necessarily specific to the biology of this protein. The suitability of the mouse model for the study of osteocalcin as a therapeutic target also appears ambiguous. With greater discrimination of the different forms of osteocalcin present in circulation and inclusion of multiple measures of bone turnover, evidence currently does not support osteocalcin as a protein critical to the diabetes and fracture association in humans.
Topics: Animals; Biomarkers; Bone and Bones; Diabetes Mellitus; Endocrine System; Humans; Models, Biological; Osteocalcin
PubMed: 25344791
DOI: 10.1007/s11892-014-0556-3 -
Archives of Biochemistry and Biophysics Nov 2014The skeleton has recently emerged as an endocrine organ implicated in the regulation of glucose and energy metabolism. This function of bone is mediated, at least in... (Review)
Review
The skeleton has recently emerged as an endocrine organ implicated in the regulation of glucose and energy metabolism. This function of bone is mediated, at least in part, by osteocalcin, an osteoblast-derived protein acting as a hormone stimulating insulin sensitivity, insulin secretion and energy expenditure. Osteocalcin secretion and bioactivity is in turn regulated by several hormonal cues including insulin, leptin, the sympathetic nervous system and glucocorticoids. Recent findings support the notion that osteocalcin functions and regulations are conserved between mice and humans. Moreover, studies in mice suggest that osteocalcin could represent a viable therapeutic approach for the treatment of obesity and insulin resistance. In this review, we summarize the current knowledge on osteocalcin functions, its various modes of action and the mechanisms implicated in the control of this hormone.
Topics: Animals; Bone and Bones; Energy Metabolism; Glucose; Homeostasis; Humans; Insulin; Insulin Resistance; Mice; Osteocalcin
PubMed: 24893146
DOI: 10.1016/j.abb.2014.05.022 -
Calcified Tissue International Jan 2015Osteocalcin is a bone-specific protein that is regularly used in the clinical setting as a serum marker of bone turnover. Recent evidence indicates that osteocalcin... (Review)
Review
Osteocalcin is a bone-specific protein that is regularly used in the clinical setting as a serum marker of bone turnover. Recent evidence indicates that osteocalcin plays a previously unsuspected role in the control of energy metabolism. Thus, osteocalcin-deficient mice have a profoundly deranged metabolic phenotype that includes insulin resistance, glucose intolerance and abnormal fat deposition. Additionally, osteocalcin administration in mice improves insulin sensitivity and decreases fat pad mass and serum triglyceride levels. The role of osteocalcin in human macronutrient metabolism is less clear but recent studies report positive correlations between serum osteocalcin levels and established indices of metabolic health. Herein, we review key physiological functions of osteocalcin, focussing on the roles of osteocalcin in the modulation of macronutrient metabolism, male reproductive function and foetal brain development. We consider the implications of these findings for the coordination of metabolism with development and fertility. We also consider evidence that a Class C G-protein-coupled receptor from a subgroup known to mediate nutrient-sensing acts as the osteocalcin receptor.
Topics: Adipose Tissue; Animals; Bone and Bones; Energy Metabolism; Humans; Osteoblasts; Osteocalcin; Peptide Hormones
PubMed: 25416346
DOI: 10.1007/s00223-014-9931-y -
Molecular Brain Mar 2019It is now generally accepted that the extra-skeleton functionalities of bone are multifaceted. Its endocrine functions came first to light when it was realized that... (Review)
Review
It is now generally accepted that the extra-skeleton functionalities of bone are multifaceted. Its endocrine functions came first to light when it was realized that osteoblasts, the bone forming cells, maintain energy homeostasis by improving glucose metabolism, insulin sensitivity and energy expenditure through osteocalcin, a multipurpose osteokine secreted by osteoblasts. Recently, the emerging knowledge on the functional aspects of this osteokine expanded to properties including adult and maternal regulation of cognitive functions. Therapeutic potential of this osteokine has also been recently reported in experimental Parkinson's disease models. This review highlights such findings on the functions of osteocalcin in the brain and emphasizes on exploring and analyzing much more in-depth basic and clinical studies.
Topics: Animals; Brain; Cognition; Humans; Motor Neuron Disease; Neuroprotective Agents; Osteocalcin; Signal Transduction
PubMed: 30909971
DOI: 10.1186/s13041-019-0444-5 -
The Journal of Clinical Investigation Feb 2022Through their ability to regulate gene expression in most organs, glucocorticoid (GC) hormones influence numerous physiological processes and are therefore key...
Through their ability to regulate gene expression in most organs, glucocorticoid (GC) hormones influence numerous physiological processes and are therefore key regulators of organismal homeostasis. In bone, GC hormones inhibit expression of the hormone Osteocalcin for poorly understood reasons. Here, we show that in a classical endocrine feedback loop, osteocalcin in return enhanced the biosynthesis of GC as well as mineralocorticoid hormones (adrenal steroidogenesis) in rodents and primates. Conversely, inactivation of osteocalcin signaling in adrenal glands significantly impaired adrenal growth and steroidogenesis in mice. Embryo-made osteocalcin was necessary for normal Sf1 expression in fetal adrenal cells and adrenal cell steroidogenic differentiation and therefore determined the number of steroidogenic cells present in the adrenal glands of adult animals. Embryonic, not postnatal, osteocalcin also governed adrenal growth, adrenal steroidogenesis, blood pressure, electrolyte equilibrium, and the rise in circulating corticosterone levels during the acute stress response in adult offspring. This osteocalcin-dependent regulation of adrenal development and steroidogenesis occurred even in the absence of a functional hypothalamus/pituitary/adrenal axis and explains why osteocalcin administration during pregnancy promoted adrenal growth and steroidogenesis and improved the survival of adrenocorticotropic hormone signaling-deficient animals. This study reveals that a bone-derived embryonic hormone influences lifelong adrenal functions and organismal homeostasis in the mouse.
Topics: Adrenal Glands; Animals; Female; Glucocorticoids; Homeostasis; Hypothalamo-Hypophyseal System; Macaca mulatta; Mice; Mice, Knockout; Osteocalcin; Pituitary-Adrenal System; Signal Transduction
PubMed: 34905510
DOI: 10.1172/JCI153752 -
The Journal of Endocrinology Apr 2021Bone is emerging as a versatile endocrine organ and its interactions with apparently unrelated organs are being more widely recognized. Osteocalcin (OCN), a polypeptide... (Review)
Review
Bone is emerging as a versatile endocrine organ and its interactions with apparently unrelated organs are being more widely recognized. Osteocalcin (OCN), a polypeptide hormone secreted by osteoblasts, has been found to exert multiple endocrine functions through its metabolically active form, uncarboxylated OCN (uOCN). Mounting evidence has shown that following its binding to G-protein coupled receptor 6a (Gprc6a) in the peripheral tissues, uOCN acts on pancreatic β cells to increase insulin secretion, and on muscle and white adipose tissue to promote glucose and lipid metabolism. More strikingly, researchers have found a surprising role of uOCN in testicular function to facilitating testosterone biosynthesis and regulating male fertility via a pancreas-bone-gonadal axis. However, the detailed functional mechanisms of uOCN on the hypothalamic-pituitary-gonadal axis or the pancreas-bone-gonadal axis are not fully understood. Besides highlighting the regulatory mechanisms of uOCN in the hypothalamus and pituitary, we also discuss its role in male as well as female fertility and its potential clinical implications in some reproductive endocrine diseases and pubertal developmental disorders.
Topics: Animals; Gonads; Humans; Hypothalamo-Hypophyseal System; Osteocalcin; Pituitary Gland
PubMed: 33760754
DOI: 10.1530/JOE-20-0203