Osteocalcin‑GPRC6A: An update of its clinical and biological multi‑organic interactions (Review)

Diaz‐Franco, Martha Cristina; León, Raúl Franco-Díaz de; Villafán-Bernal, José Rafael

doi:10.3892/mmr.2018.9627

Cited by 23 publications

(33 citation statements)

References 59 publications

(59 reference statements)

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“…This protein has also an effect in the control of bone mass, with positive effects on cortical mineral density. It is also demonstrated that irisin plays a crucial role in the reduction of sarcopenia in old people [55,56]. Osteocalcin is a bone-derived hormone-like protein.…”

Section: Discussionmentioning

confidence: 99%

Physical Activity for the Treatment of Chronic Low Back Pain in Elderly Patients: A Systematic Review

Vadalà

Russo

Salvatore

et al. 2020

JCM

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Chronic low back pain (CLBP) affects nearly 20–25% of the population older than 65 years, and it is currently the main cause of disability both in the developed and developing countries. It is crucial to reach an optimal management of this condition in older patients to improve their quality of life. This review evaluates the effectiveness of physical activity (PA) to improve disability and pain in older people with non-specific CLBP. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used to improve the reporting of the review. Individual risk of bias of single studies was assessed using Rob 2 tool and ROBINS-I tool. The quality of evidence assessment was performed using GRADE analysis only in articles that presents full data. The articles were searched in different web portals (Medline, Scopus, CINAHL, EMBASE, and CENTRAL). All the articles reported respect the following inclusion criteria: patients > 65 years old who underwent physical activities for the treatment of CLBP. A total of 12 studies were included: 7 randomized controlled trials (RCT), 3 non-randomized controlled trials (NRCT), 1 pre and post intervention study (PPIS), and 1 case series (CS). The studies showed high heterogeneity in terms of study design, interventions, and outcome variables. In general, post-treatment data showed a trend in the improvement for disability and pain. However, considering the low quality of evidence of the studies, the high risk of bias, the languages limitations, the lack of significant results of some studies, and the lack of literature on this argument, further studies are necessary to improve the evidences on the topic.

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Section: Discussionmentioning

confidence: 99%

Physical Activity for the Treatment of Chronic Low Back Pain in Elderly Patients: A Systematic Review

Vadalà

Russo

Salvatore

et al. 2020

JCM

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“…For example, mutations in the Phex gene are connected with rachitic changes in the bone growth plate, and this effect is mimicked by caspase inhibitors 36 . Osteocalcin is clinically important not only in bone regulation but also in many other tissues where it has a mediating role 37 . The regulation of Phex expression by caspase inhibition was described for the first time as was the specification of individual caspases in osteocalcin and Phex pathways.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic impact of pro-apoptotic caspase inhibitors in MC3T3-E1 cells

Kratochvílová

Veselá

Ledvina

et al. 2020

Sci Rep

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Caspases are proteases traditionally associated with inflammation and cell death. Recently, they have also been shown to modulate cell proliferation and differentiation. The aim of the current research was to search for osteogenic molecules affected by caspase inhibition and to specify the individual caspases critical for these effects with a focus on proapoptotic caspases: caspase-2,-3,-6,-7,-8 and-9. Along with osteocalcin (Ocn), general caspase inhibition significantly decreased the expression of the Phex gene in differentiated MC3T3-E1 cells. The inhibition of individual caspases indicated that caspase-8 is a major contributor to the modification of Ocn and Phex expression. Caspase-2 and-6 had effects on Ocn and caspase-6 had an effect on Phex. These data confirm and expand the current knowledge about the nonapoptotic roles of caspases and the effect of their pharmacological inhibition on the osteogenic potential of osteoblastic cells. Caspases are proteases that are currently associated with inflammation and cell death. Their use has broad implications for pathological conditions, such as cancer and degenerative disorders. Caspase inhibitors have been tested in several therapeutic approaches 1. Additionally, a much broader spectrum of caspase functions has been demonstrated 2 , particularly proapoptotic caspases, including apical caspases-8 and-9, the executive trio of caspase-3,-6 and-7 and the still enigmatic caspase-2. New functions of caspases have also been reported in osteogenesis 3,4. Bmp4-induced differentiation of osteoblastic MC3T3-E1 cells leads to the activation of caspase-2,-3 and-8 without increasing the apoptosis rate 5. Pharmaceutical inhibition of caspases reduced Alp activity in MC3T3-E1 cells and the expression levels of osteocalcin, a molecule typically found in osteoblasts 4,5. Notably, osteocalcin is also used in medical diagnoses as a biochemical marker of bone formation and metabolic risk 6. Pharmacological caspase inhibitors are considered potential tools in several therapies 1. Previous works have focused on the alteration of gene expression during MC3T3-E1 cell differentiation 7,8 , which consists of several phases, including proliferation, differentiation and matrix deposition, accompanied by the production of specific osteogenic factors 9. Since these phases were first characterized 10 , hundreds of reports have been based on experiments performed using MC3T3-E1 cells. Given their intramembranous origin, MC3T3-E1 cells are recognized as suitable in vitro models for direct osteoblastic differentiation and pleiotropic studies 11. Based on published results and our preliminary data, we hypothesized that proapoptotic caspases impact gene expression in differentiated MC3T3-E1 cells. The following investigation addresses the effects of caspase blockade on gene expression in differentiated cells. For the first time, a cell bioluminescence-based approach was used to record the activation of individual proapoptotic caspases during MC3T3-E1 cell cultivation. Therefore, the osteogenic profi...

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“…The main bone-derived mediator affecting the brain represents osteocalcin (OCN), which is encoded by the BGLAP gene and exclusively synthesized by osteoblasts. Undercarboxylated, bioactive OCN, initially considered as an inhibitor of bone mineralization [ 337 ], participates in systemic body regulation and homeostasis [ 338 ] primarily regulating insulin secretion, muscle adaptation as well as testosterone production in the testis [ 6 ]. In addition, OCN was recently discovered to transverse the BBB to enter the CNS, where it promotes spatial learning and memory while preventing anxiety-like behavior or even depression [ 6 ].…”

Section: Molecular Bases Of Brain-bone Crosstalkmentioning

confidence: 99%

Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases

Otto

Knapstein

Jahn

et al. 2020

IJMS

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As brain and bone disorders represent major health issues worldwide, substantial clinical investigations demonstrated a bidirectional crosstalk on several levels, mechanistically linking both apparently unrelated organs. While multiple stress, mood and neurodegenerative brain disorders are associated with osteoporosis, rare genetic skeletal diseases display impaired brain development and function. Along with brain and bone pathologies, particularly trauma events highlight the strong interaction of both organs. This review summarizes clinical and experimental observations reported for the crosstalk of brain and bone, followed by a detailed overview of their molecular bases. While brain-derived molecules affecting bone include central regulators, transmitters of the sympathetic, parasympathetic and sensory nervous system, bone-derived mediators altering brain function are released from bone cells and the bone marrow. Although the main pathways of the brain-bone crosstalk remain ‘efferent’, signaling from brain to bone, this review emphasizes the emergence of bone as a crucial ‘afferent’ regulator of cerebral development, function and pathophysiology. Therefore, unraveling the physiological and pathological bases of brain-bone interactions revealed promising pharmacologic targets and novel treatment strategies promoting concurrent brain and bone recovery.

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Osteocalcin‑GPRC6A: An update of its clinical and biological multi‑organic interactions (Review)

Cited by 23 publications

References 59 publications

Physical Activity for the Treatment of Chronic Low Back Pain in Elderly Patients: A Systematic Review

Physical Activity for the Treatment of Chronic Low Back Pain in Elderly Patients: A Systematic Review

Osteogenic impact of pro-apoptotic caspase inhibitors in MC3T3-E1 cells

Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases

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