Irisiini myokiini, josta muodostuu treenauksissa . Mikä sen merkitys on?

https://sv.wikipedia.org/wiki/Irisin

Irisin eller fibronectin type III domain containing 5^[1] (FRCP2) är ett kroppseget protein, som påverkar fettomsättning och glukosomsättning. Irisin definieras som en myokin, det vill säga ett slags cytokin, samt ett adipokin.^[2][3]
Irisin kodas av en gen som finns lokaliserad på 1p35.1. Proteinet, som består av 212 aminosyror, utsöndras från muskelceller och utsöndringen ökar när musklerna används vid träning. Det verkar också i både vita och bruna fettceller, och tycks påverka bildning av de bruna fettcellerna. Vid träning ökar mängden irisin i serum något, vilket påverkar energiförbrukning och minskar fetma hos möss.^[4][5] Träning och fysisk aktivitet verkar påverka irisinnivåerna direkt genom en stegring, men stegringen är snabbt övergående och nivåerna har stabiliserats efter 90 min.^[6] Irisin verkar också vara ett adipokin som utsöndras från fettceller.^[3] Genom sin påverkan på brunt fett, verkar det termoreglerande.^[7]
Irisin finns också uttryckt i hjärtat, samt i lägre grad i tarmen, mjälten och bukspottkörteln.^[8] Det tycks finnas ett samband mellan irisinnivåer och tyroidstatus (sköldkörteln, TSH och tyroxin), med ett negativt samband mellan irisin och TSH. Hos hypotyroida är cirkulerande irisin i serum lägre och hos hypertyroida högre.^[7]
När irisin visade sig öka vid träning och påverka termoreglering och ämnesomättning, framställdes det allmänt som ett kommande medel mot diverse livsstilssjukdomar som man sett i västvärlden.^[9] Minskad irisinaktivitet förekommer vid t.ex. insulinresistens och typ 2-diabetes, tillstånd som bevisligen förbättras av träning.^[10] Dock har forskning också lett till tvivel att irisinets påverkan och utsöndring är generellt lika för olika åldrar och för dem som är i olika kondition.^[11] Irisinaktiviteten kan t.ex. förändras vid hjärtsvikt, och kan eventuellt hänga samman med den träningsintolerans som ses vid tillståndet.^[12] Å andra sidan finns studier som tyder på att irisinnivåerna inte förändras av att bli mera vältränad, så när som på den direkta effekten av den akuta stegringen vid träningspasset.^[13]
Irisin är ett av moderns kroppsegna ämnen som överförs via bröstmjölk till barnet, vilket antyder att det därvidlag deltar i att reglera barnets tillväxt och ämnesomsättning. Mängden irisin i bröstmjölken påverkas av huruvida modern lider av graviditetsdiabetes eller inte.^[14]

Rangan treenaus ja RANKL

Treenaus vaikuttaa myokiinin irisiinin eritystä.Tämänniminen myokiini on taas minulle uusi molekyyli. Otan kuvan asiasta.  Se vaikuttaa  RANKL  tien hiljenemistä ja sen sijaan osteobalstien  kypsymistä  ja  rasvakudoksen muuttumista  ruskeampaan rasvakudostyyliin, joka pystyy luomaan energiaa ja lämpöä.
  https://www.nature.com/bonekeyreports/2016/160720/bonekey201648/fig_tab/bonekey201648_F3.html

https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcQ1P84glL0OhbiArGMyw3tz99pltor6lUq8OHpl7_ffofp0aS-g

RANKL geeni, TNFSF11 (13q14.11), ODF, OPGL, CD254, OPTB2, TNLG6B, TRANCE, hRANKL2

 Luustometabolian yhteydessä tämä RANKL-geeninimi lie useiten käytössä.  Synonyymejä on monta.
https://www.ncbi.nlm.nih.gov/gene/8600

Also known as

ODF; OPGL; sOdf; CD254; OPTB2; RANKL; TNLG6B; TRANCE; hRANKL2

 

 

Summary (Suomennosta)

Tämä geeni koodaa TNF- sytokiiniperheen jäsentä, joka toimii  osteoprotegeriinin ligandina ja  on  avain tekijä osteokalstein erilaistumisessa ja aktivoitumisessa.  Tämä RANKL- proteiini näyttää olevan  dendriittisolujen elossapysymisfaktori ja se osallistuu T-solusta riippuvaiseen immuunivasteeseen.  T-solujen aktivoituminen indusoi RANKL- geenin ilmenemän ja johtaa lisäntyneeseen osteoklastigeneesiin ja luukatoon.  Tämä proteiini  näyttää aktivoivan  antiapoptoottisen kinaasin AKT/PKB:n  Srckinaasi/TRAF6-signaalikompleksin  kautta, mikä  viittaa siihen, että tällä proteiinilla on  osuutta  solun apoptoosin säätelyssä.  Jos hiirellä  kohdennetusti  tätä proteiinia  vastaava geeni irrotetaan, seuraa vaikea osteopetroosi ja  osteoklastien puute. Geenipuutteinen hiiri ilmentää  T- ja B-imusolujen varhaiserilaistumisen defektejä ja raskauden aikana siltä puuttui kyky muodosta lobuloalveolaarista   rintarauhasstruktuuria. Geenistä on kaksi  vaihtoehtoispleissauksella syntyvää transkriptia. Geeniä ilmenee  imusolmukkeisssa, umpilisäkkeessä  ja 6 muussa kudoksessa.

This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found. [provided by RefSeq, Jul 2008]

Expression

Biased expression in lymph node (RPKM 4.9), appendix (RPKM 2.0) and 6 other tissues See more

(Lisätietoja)  Related articles in PubMed

1. The Expression of Matrix Metalloproteinases in Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-expressing Cancer of Apocrine Origin. Kambayashi Y, et al. Anticancer Res, 2018 Jan. PMID 29277763
2. Effects of Osteogenic-Conditioned Medium from Human Periosteum-Derived Cells on Osteoclast Differentiation. Park HC, et al. Int J Med Sci, 2017. PMID 29200953, Free PMC Article
3. RANKL-mediated harmonious dialogue between fetus and mother guarantees smooth gestation by inducing decidual M2 macrophage polarization. Meng YH, et al. Cell Death Dis, 2017 Oct 12. PMID 29022922, Free PMC Article
4. Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort. Sarink D, et al. Cancer Prev Res (Phila), 2017 Sep. PMID 28701332, Free PMC Article
5. -643C > T RANKL gene polymorphism is associated with osteoporosis in Tunisian postmenopausal women. Sassi R, et al. Climacteric, 2017 Aug. PMID 28453307

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. The -643C>T RANKL polymorphism, through its significant influence on body weight and BMI value, may contribute to the development of Osteoporosis in Postmenopausal women.
2. In the present study, we measured expression of RANKL in human periosteum-derived cells(hPDCs) undergoing osteoblastic differentiation and found that expression of RANKL mRNA was markedly increased in these cells in a time-dependent manner.RANKL protein expression was also significantly enhanced in osteogenic-conditioned media from hPDCs undergoing osteoblastic differentiation
3. MiR-217 is a useful diagnostic biomarker and is involved in human podocyte cells apoptosis via targeting TNFSF11 in membranous nephropathy.
4. rs9525641 might contribute to bone mineral density
5. Vascular smooth cells are a significant source of osteoprotegerin within the vasculature but that RANKL, once present, downregulates this production and appears capable of preventing the "protective" upregulation of OPG seen with VSMCs exposed to physiological levels of cyclic strain.
6. receptor activator for nuclear factor-kappa B ligand (RANKL), secreted by human embryonic trophoblasts and maternal decidual stromal cells, polarizes decidual macrophages toward a M2 phenotype.
7. There were no significant associations involving the RANKL gene. Thus, it is suggested that alterations in the OPG and RANK genes are primarily responsible for altering the function and expression of the RANKL ligand, resulting in a predisposition to chronic arthralgia and comorbid temporomandibular OA.
8. Vitamin D, tumor necrosis factor (TNF)-alpha, receptor activator of nuclear factor-KB ligand (RANKL), and OPG levels were determined in GCF and serum. Baseline clinical parameters were similar in all periodontitis groups (P > 0.05) but were higher than that in controls
9. study demonstrated the association of the -643C > T polymorphism with bone mineral density variation and osteoporosis risk in postmenopausal Tunisian women
10. down-regulated miR-143-5p promotes the differentiation of DPSCs into odontoblasts by enhancing Runx2 expression via the OPG/RANKL signaling pathway.

Luuston osuus systeemisessä endokriinisessä säätelyssä

Luuston osallistuminen  systeemiseen endokriiniseen säätelyyn

https://www.ncbi.nlm.nih.gov/pubmed/30044111

Physiol Res. 2018 Jul 25. [Epub ahead of print]

Involvement of bone in systemic endocrine regulation.

Zofkova I¹. Abstract (Suomennosta) 

Luuston osuus on epäsovinnainen  ihmisorganissin fysiologiassa ja patofysiologiassa - ei vain siksi että se on lukuisten systeemisten hormonien kohde,  vaan  se on myös endokriininen kudos, joka moduloi luustosysteemiä  ja luuston ulkopuolisia systeemejä. Tästä näkökannasta  luuostn pääsoluja ovat OSTEOSYYTIT.   Nämä solut  toimivat  pääasiallisesti mekanosensoreina ja mopduloivat luun uudelleenmuotoutumista.  Jos osteosyytit jäävät mekaanista kuormitusta vaille, ne alkavat  syntetisoida SKLEROSTIINIA, joka taas on  vahva luunmuodostuksen estäjä ja RANKL:ia, joka on  vahva luun resorboitumisen aktivaattori.

• The skeleton shows an unconventional role in the physiology and pathophysiology of the human organism, not only as the target tissue for a number of systemic hormones, but also as endocrine tissue modulating some skeletal and extraskeletal systems. From this point of view, the principal cells in the skeleton are osteocytes. These cells primarily work as mechano-sensors and modulate bone remodeling. Mechanically unloaded osteocytes synthetize sclerostin, the strong inhibitor of bone formation and RANKL, the strong activator of bone resorption. 

 OSTEOSYYTIT ilmentävät myös aktiivia D- vitamiinia  (D(1,25(OH)2)D ja FOSFATONIINIA, kuten FGF23.  On havaittu, että aktiivi D-vitamiini ja FGF23 ovat fosfaattiaineenvaihdunnan  voimakkaat säätelijät, myös  kroonisessa  munuaistaudissa huomioitavia.

• Osteocytes also express hormonally active vitamin D (1,25(OH)(2) D) and phosphatonins, such as FGF23. Both 1,25(OH)(2) D and FGF23 have been identified as powerful regulators of the phosphate metabolism, including in chronic kidney disease.

OSTEOBLASTIT ovat myös  luuston endokriinisiä soluja, jotka osallistuvat luun uudelleenmuodostamiseen. Kun FGF23  kohdistaa munuaisiin ja lisäkilpirauhaseen kontrolloidessaan  D-vitamiinin ja fosfaattien aineenvaihduntaa, niin osteoblastit ilmentävät KALSITONIINIA, joka pystyy moduloimaan GPRC6A-reseptorivälitteisesti  haimasaarekkeiden betasoluja, lihasta, rasvakudosta, aivoja ja testiksiä.

•  Further endocrine cells of the skeleton involved in bone remodeling are osteoblasts. While FGF23 targets the kidney and parathyroid glands to control metabolism of vitamin D and phosphates, osteoblasts express osteocalcin, which through GPRC6A receptors modulates beta cells of the pancreatic islets, muscle, adipose tissue, brain and testes.

Tässä otsikon artikkelissa tehdään katsausta  luun hormonaalisen verkoston ja fosfaatti- tai energiahomeostaasin  ja/tai  maskuliinisen  reproduktion välisestä  interaktiosta.

• This article reviews some knowledge concerning the interaction between the bone hormonal network and phosphate or energy homeostasis and/or male reproduction.

SOST geeni on restriktiivisesti munuaisessa sijaitseva.

Tästä sijainnista  tulee mieleen munuaistaudit ja yhteys sklerostiiniin tai munuais tranaplantaatiotilanne. Lisäksi  suhde D-vitamiinin aktivoitumiseen. Uusimmissa artikkelissa näyttää olevan  lisätietoa näistä aihepiireistä.
Lisäksi on hyvää artikkelia osteosyytin mekanobiologiasta.
Osteosyytit erittävät tätä sklerostiinia.  Tässä vain tämä suhde  geenin restriktiivisen  munuaisperäiseen sijaintiin ( vähän myös keuhkossa staappelidiagramman mukaan) herättää erinäisiä kysymyksiä, joihin etsin vastauksia lähiaikoina.

SOST geeni ja sen tuote sklerostiini. Uutta tietoa vuodelta 2017

SOST gene (17q21.31), Sclerostin

https://www.ncbi.nlm.nih.gov/protein/NP_079513.1

GenPept

sclerostin precursor [Homo sapiens]

NCBI Reference Sequence: NP_079513.1

Identical Proteins FASTA Graphics

Go to:

LOCUS       NP_079513                213 aa            linear   PRI 23-JUN-2018
DEFINITION  sclerostin precursor [Homo sapiens].
ACCESSION   NP_079513
VERSION     NP_079513.1
DBSOURCE    REFSEQ: accession NM_025237.2
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 213)
  AUTHORS   Wu T, Wang LN, Tang DR and Sun FY.
  TITLE     SOST silencing promotes proliferation and invasion and reduces
            apoptosis of retinoblastoma cells by activating Wnt/beta-catenin
            signaling pathway
  JOURNAL   Gene Ther. 24 (7), 399-407 (2017)
   PUBMED   28485721
  REMARK    GeneRIF: SOST silencing promotes the proliferation, invasion and
            migration, and decreases the apoptosis of human retinoblastoma
            cells by activating the Wnt/beta-catenin signaling pathway.
REFERENCE   2  (residues 1 to 213)
  AUTHORS   Tartaglione L, Pasquali M, Rotondi S, Muci ML, Leonangeli C,
            Farcomeni A, Fassino V and Mazzaferro S.
  TITLE     Interactions of sclerostin with FGF23, soluble klotho and vitamin D
            in renal transplantation
  JOURNAL   PLoS ONE 12 (5), e0178637 (2017)
   PUBMED   28558021
  REMARK    GeneRIF: Sclerostin levels in KTR are normal and influenced more by
            bone turnover than by eGFR. Its involvement with other hormones of
            mineral homeostasis (FGF23/Klotho and Vitamin D) is part of the
            sophisticated cross-talk between bone and the kidney
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 213)
  AUTHORS   Behets GJ, Viaene L, Meijers B, Blocki F, Brandenburg VM, Verhulst
            A, D'Haese PC and Evenepoel P.
  TITLE     Circulating levels of sclerostin but not DKK1 associate with
            laboratory parameters of CKD-MBD
  JOURNAL   PLoS ONE 12 (5), e0176411 (2017)
   PUBMED   28493902
  REMARK    GeneRIF: In chronic kidney disease, serum levels of the Wnt
            inhibitors DKK1 and sclerostin are unrelated, indicating different
            sites of origin and/ or different regulatory mechanisms.
            Sclerostin, as opposed to DKK1, may qualify as a biomarker of
            chronic kidney disease-mineral and bone and mineral disorder
            (CKD-MBD), particularly in dialysis patients.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 213)
  AUTHORS   Saritekin I, Acikgoz S, Bayraktaroglu T, Kuzu F, Can M, Guven B,
            Mungan G, Buyukuysal C and Sarikaya S.
  TITLE     Sclerostin and bone metabolism markers in hyperthyroidism before
            treatment and interrelations between them
  JOURNAL   Acta Biochim. Pol. 64 (4), 597-602 (2017)
   PUBMED   29059259
  REMARK    GeneRIF: No difference was found in the serum sclerostin levels
            between the hyperthyroidism patients and healthy control.
REFERENCE   5  (residues 1 to 213)
  AUTHORS   Shi J, Ying H, Du J and Shen B.
  TITLE     Serum Sclerostin Levels in Patients with Ankylosing Spondylitis and
            Rheumatoid Arthritis: A Systematic Review and Meta-Analysis
  JOURNAL   Biomed Res Int 2017, 9295313 (2017)
   PUBMED   28553652
  REMARK    GeneRIF: The difference of serum sclerostin levels in Ankylosing
            Spondylitis and Rheumatoid Arthritis patients was not significantly
            different from HC, indicating that the sclerostin may not associate
            with the development of Ankylosing Spondylitis and Rheumatoid
            Arthritis.
            Review article
            Erratum:[Biomed Res Int. 2017;2017:3953474. PMID: 29181394]
REFERENCE   6  (residues 1 to 213)
  AUTHORS   Staehling-Hampton K, Proll S, Paeper BW, Zhao L, Charmley P, Brown
            A, Gardner JC, Galas D, Schatzman RC, Beighton P, Papapoulos S,
            Hamersma H and Brunkow ME.
  TITLE     A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21
            is associated with van Buchem disease in the Dutch population
  JOURNAL   Am. J. Med. Genet. 110 (2), 144-152 (2002)
   PUBMED   12116252
REFERENCE   7  (residues 1 to 213)
  AUTHORS   Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C,
            Dioszegi M, Dikkers FG, Hildering P, Willems PJ, Verheij JB,
            Lindpaintner K, Vickery B, Foernzler D and Van Hul W.
  TITLE     Identification of a 52 kb deletion downstream of the SOST gene in
            patients with van Buchem disease
  JOURNAL   J. Med. Genet. 39 (2), 91-97 (2002)
   PUBMED   11836356
  REMARK    GeneRIF: A 52 kb deletion has been identified downstream of the
            SOST gene in patients with van Buchem disease.
REFERENCE   8  (residues 1 to 213)
  AUTHORS   Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M,
            Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves AF, Hill S,
            Bueno M, Ramos FJ, Tacconi P, Dikkers FG, Stratakis C, Lindpaintner
            K, Vickery B, Foernzler D and Van Hul W.
  TITLE     Increased bone density in sclerosteosis is due to the deficiency of
            a novel secreted protein (SOST)
  JOURNAL   Hum. Mol. Genet. 10 (5), 537-543 (2001)
   PUBMED   11181578
REFERENCE   9  (residues 1 to 213)
  AUTHORS   Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll
            S, Skonier JE, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert
            T, Tacconi P, Galas D, Hamersma H, Beighton P and Mulligan J.
  TITLE     Bone dysplasia sclerosteosis results from loss of the SOST gene
            product, a novel cystine knot-containing protein
  JOURNAL   Am. J. Hum. Genet. 68 (3), 577-589 (2001)
   PUBMED   11179006
REFERENCE   10 (residues 1 to 213)
  AUTHORS   Beighton,P.H., Hamersma,H. and Brunkow,M.E.
  TITLE     SOST-Related Sclerosing Bone Dysplasias
  JOURNAL   (in) Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens
            K and Amemiya A (Eds.);
            GENEREVIEWS((R));
            (1993)
   PUBMED   20301406
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF326739.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: Sclerostin is a secreted glycoprotein with a C-terminal
            cysteine knot-like (CTCK) domain and sequence similarity to the DAN
            (differential screening-selected gene aberrative in neuroblastoma)
            family of bone morphogenetic protein (BMP) antagonists.
            Loss-of-function mutations in this gene are associated with an
            autosomal-recessive disorder, sclerosteosis, which causes
            progressive bone overgrowth. A deletion downstream of this gene,
            which causes reduced sclerostin expression, is associated with a
            milder form of the disorder called van Buchem disease. [provided by
            RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF326739.1, AY358627.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1970526, SAMEA2142363
                                           [ECO:0000348]
            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..213
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17q21.31"
     Protein         1..213
                     /product="sclerostin precursor"
                     /calculated_mol_wt=21522
     sig_peptide     1..23
                     /inference="COORDINATES: ab initio prediction:SignalP:4.0"
                     /calculated_mol_wt=2526
     mat_peptide     24..213
                     /product="sclerostin"
                     /calculated_mol_wt=21522
     Region          28..210
                     /region_name="GHB_like"
                     /note="Glycoprotein hormone beta chain homologues;
                     cl21545"
                     /db_xref="CDD:328788"
     CDS             1..213
                     /gene="SOST"
                     /gene_synonym="CDD; DAND6; SOST1; VBCH"
                     /coded_by="NM_025237.2:48..689"
                     /db_xref="CCDS:CCDS11468.1"
                     /db_xref="GeneID:50964"
                     /db_xref="HGNC:HGNC:13771"
                     /db_xref="MIM:605740"
ORIGIN      
        1 mqlplalclv cllvhtafrv vegqgwqafk ndateiipel geypepppel ennktmnrae
       61 nggrpphhpf etkdvseysc relhftryvt dgpcrsakpv telvcsgqcg parllpnaig
      121 rgkwwrpsgp dfrcipdryr aqrvqllcpg geaprarkvr lvasckckrl trfhnqselk
      181 dfgteaarpq kgrkprprar sakanqaele nay
//

NIVelRUSTOSTA terminologiaa

https://www.sciencedirect.com/science/article/pii/S0378111917305127
Tässä artikkelissa on kerrottu nivelrustotutkimusksita ja termejä on paljon. Myös useita ZNF mainitaan, jokunen TRIM ja RNF. Lopuksi myös ISG15 ubiquitin like modifier.
12.6. 2018