Abstract:For the first time, we show that Cry 2 rs2292910 and MTNR1B rs3781638 are associated with osteoporosis in a Chinese geriatric cohort. Therefore, targeting the abnormalities of the CRY2 and MTNR1B genes may be a potential strategy to treat and/or to prevent osteoporosis.
“…124 Curiously, lipocalin 2, a recently identified ligand of MC4R, is secreted by osteoblasts in mice and signals to suppress appetite by binding MC4R-expressing hypothalamic neurons 125 ; MC4R polymorphisms have also been associated with early-onset obesity. 126 Mutation of CNR2 21 and MTNR1B 127 had an additional association with human osteoporosis. Karsak et al found that two missense variants (the double single-nucleotide polymorphism (SNP) rs2502992–rs2501432 and Gln63Arg; rs2229579 and His316Tyr) are associated with osteoporosis in postmenopausal Caucasian women, 21 while Li et al found that MTNR1B rs3781638 is associated with osteoporosis in Chinese geriatrics.…”
Section: Diseases or Dysfunction Caused By Gpcr Mutation Or Deletion mentioning
confidence: 99%
“…Karsak et al found that two missense variants (the double single-nucleotide polymorphism (SNP) rs2502992–rs2501432 and Gln63Arg; rs2229579 and His316Tyr) are associated with osteoporosis in postmenopausal Caucasian women, 21 while Li et al found that MTNR1B rs3781638 is associated with osteoporosis in Chinese geriatrics. 127 The ADRB2 polymorphism (rs1042714) was also associated with heterotopic ossification in adult trauma patients with fractures. 128 EDG2 26 and H4R 23 were associated with human osteoarthritis (OA) in Japanese people.…”
Section: Diseases or Dysfunction Caused By Gpcr Mutation Or Deletion mentioning
The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals. Critical roles of GPCRs have been established in bone development, remodeling, and disease. Multiple human GPCR mutations impair bone development or metabolism, resulting in osteopathologies. Here we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in animals. To date, 92 receptors (5 glutamate family, 67 rhodopsin family, 5 adhesion, 4 frizzled/taste2 family, 5 secretin family, and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals). By analyzing data from these 92 GPCRs, we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions, and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal models. Data from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD: 9 genes each for human height and osteoporosis; 4 genes each for human osteoarthritis (OA) and fracture risk; and 2 genes each for adolescent idiopathic scoliosis (AIS), periodontitis, osteosarcoma growth, and tooth development. Reports from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass, while deficiency of 22 GPCRs increased bone mass and BMD; deficiency of 8 GPCRs reduced body length, while 5 mice had reduced femur size upon GPCR deletion. Furthermore, deficiency in 6 GPCRs induced osteoporosis; 4 induced osteoarthritis; 3 delayed fracture healing; 3 reduced arthritis severity; and reduced bone strength, increased bone strength, and increased cortical thickness were each observed in 2 GPCR-deficiency models. The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis, population studies, and investigation of phenotype correlation with SNPs to elucidate GPCR function in human diseases.
“…124 Curiously, lipocalin 2, a recently identified ligand of MC4R, is secreted by osteoblasts in mice and signals to suppress appetite by binding MC4R-expressing hypothalamic neurons 125 ; MC4R polymorphisms have also been associated with early-onset obesity. 126 Mutation of CNR2 21 and MTNR1B 127 had an additional association with human osteoporosis. Karsak et al found that two missense variants (the double single-nucleotide polymorphism (SNP) rs2502992–rs2501432 and Gln63Arg; rs2229579 and His316Tyr) are associated with osteoporosis in postmenopausal Caucasian women, 21 while Li et al found that MTNR1B rs3781638 is associated with osteoporosis in Chinese geriatrics.…”
Section: Diseases or Dysfunction Caused By Gpcr Mutation Or Deletion mentioning
confidence: 99%
“…Karsak et al found that two missense variants (the double single-nucleotide polymorphism (SNP) rs2502992–rs2501432 and Gln63Arg; rs2229579 and His316Tyr) are associated with osteoporosis in postmenopausal Caucasian women, 21 while Li et al found that MTNR1B rs3781638 is associated with osteoporosis in Chinese geriatrics. 127 The ADRB2 polymorphism (rs1042714) was also associated with heterotopic ossification in adult trauma patients with fractures. 128 EDG2 26 and H4R 23 were associated with human osteoarthritis (OA) in Japanese people.…”
Section: Diseases or Dysfunction Caused By Gpcr Mutation Or Deletion mentioning
The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals. Critical roles of GPCRs have been established in bone development, remodeling, and disease. Multiple human GPCR mutations impair bone development or metabolism, resulting in osteopathologies. Here we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in animals. To date, 92 receptors (5 glutamate family, 67 rhodopsin family, 5 adhesion, 4 frizzled/taste2 family, 5 secretin family, and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals). By analyzing data from these 92 GPCRs, we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions, and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal models. Data from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD: 9 genes each for human height and osteoporosis; 4 genes each for human osteoarthritis (OA) and fracture risk; and 2 genes each for adolescent idiopathic scoliosis (AIS), periodontitis, osteosarcoma growth, and tooth development. Reports from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass, while deficiency of 22 GPCRs increased bone mass and BMD; deficiency of 8 GPCRs reduced body length, while 5 mice had reduced femur size upon GPCR deletion. Furthermore, deficiency in 6 GPCRs induced osteoporosis; 4 induced osteoarthritis; 3 delayed fracture healing; 3 reduced arthritis severity; and reduced bone strength, increased bone strength, and increased cortical thickness were each observed in 2 GPCR-deficiency models. The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis, population studies, and investigation of phenotype correlation with SNPs to elucidate GPCR function in human diseases.
“…Moreover, mice lacking CRY1 and CRY2 exhibit increased bone volume [ 91 ]. In a Chinese pediatric cohort, Cry2 rs2292910 was associated with osteoporosis (r = -0.082, p = 0.045) [ 96 ].…”
Numerous physiological processes of mammals, including bone metabolism, are regulated by the circadian clock system, which consists of a central regulator, the suprachiasmatic nucleus (SCN), and the peripheral oscillators of the BMAL1/CLOCK-PERs/CRYs system. Various bone turnover markers and bone metabolism-regulating hormones such as melatonin and parathyroid hormone (PTH) display diurnal rhythmicity. According to previous research, disruption of the circadian clock due to shift work, sleep restriction, or clock gene knockout is associated with osteoporosis or other abnormal bone metabolism, showing the importance of the circadian clock system for maintaining homeostasis of bone metabolism. Moreover, common causes of osteoporosis, including postmenopausal status and aging, are associated with changes in the circadian clock. In our previous research, we found that agonism of the circadian regulators REV-ERBs inhibits osteoclast differentiation and ameliorates ovariectomy-induced bone loss in mice, suggesting that clock genes may be promising intervention targets for abnormal bone metabolism. Moreover, osteoporosis interventions at different time points can provide varying degrees of bone protection, showing the importance of accounting for circadian rhythms for optimal curative effects in clinical treatment of osteoporosis. In this review, we summarize current knowledge about circadian rhythms and bone metabolism.
“…To be able to understand the role of the circadian clock system thoroughly, not only presence and function have to be investigated, but also demonstrating consequences of dysregulation is of importance. Interruption of the circadian clock mechanisms gave hints to implications in various diseases as diabetes [12, 13], osteoporosis [14], cancer [15] and immune-allergic diseases [16]. Finding the links between the circadian clock and diseases is of particular importance these days, since modern living comes along with numerous factors, which disturb circadian rhythms: artificial light of different sources being available at all times, irregular food uptake, shift work and so on.Fig.…”
Molecular clocks help organisms to adapt important physiological functions to periodically changing conditions in the environment. These include the adaption of the 24 h sleep-wake rhythm to changes of day and night. The circadian clock is known to act as a key regulator in processes of health and disease in different organs. The knowledge on the circadian clock led to the development of chronopharmacology and chronotherapy. These fields aim to investigate how efficiency of medication and therapies can be improved based on circadian clock mechanisms. In this review we aim to highlight the role of the circadian clock in oral tissues and its potential in the different fields of dentistry including oral and maxillofacial surgery, restorative dentistry, endodontics, periodontics and orthodontics to trigger the evolving field of chronodentistry.
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