Sclerostin expression and functions beyond the osteocyte

Weivoda, Megan M.; Youssef, Stephanie J.; Oursler, Merry Jo

doi:10.1016/j.bone.2016.11.024

Cited by 111 publications

(95 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These observations suggest that Wnt and insulin signaling in WAT are associated and that lower Wnt signaling might, at least in part, affect insulin signaling in South Asians. Sclerostin is a glycoprotein produced predominantly by mature osteocytes within the mineralized bone matrix, that negatively regulates bone formation via inhibiting canonical Wnt signaling [21,22]. We observed higher sclerostin levels in South Asians compared with white Caucasians.…”

Section: Discussionmentioning

confidence: 58%

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

et al. 2020

View full text Add to dashboard Cite

Background: South Asians generally have an unfavourable metabolic phenotype compared with white Caucasians, including central obesity and insulin resistance. The Wnt protein family interacts with insulin signaling, and impaired Wnt signaling is associated with adiposity and type 2 diabetes mellitus. We aimed to investigate Wnt signaling in relation to insulin signaling in South Asians compared with white Caucasians. Methods: Ten Dutch South Asian men with prediabetes and overweight or obesity and 10 matched Dutch white Caucasians were included. Blood samples were assayed for the Wnt inhibitor sclerostin. Subcutaneous white adipose tissue (WAT) and skeletal muscle biopsies were assayed for Wnt and insulin signaling gene expression with quantitative reverse transcription polymerase chain reaction (Clinicaltrials.gov NCT02291458). Results: Plasma sclerostin was markedly higher in South Asians compared with white Caucasians (+65%, P<0.01). Additionally, expression of multiple Wnt signaling genes and key insulin signaling genes were lower in WAT in South Asians compared with white Caucasians. Moreover, in WAT in both ethnicities, Wnt signaling gene expression strongly positively correlated with insulin signaling gene expression. In skeletal muscle, WNT10B expression in South Asians was lower, but expression of other Wnt signaling and insulin signaling genes was comparable between ethnicities. Wnt and insulin signaling gene expression also positively correlated in skeletal muscle, albeit less pronounced. Conclusion: South Asian men with overweight or obesity and prediabetes have higher plasma sclerostin and lower Wnt signaling gene expression in WAT compared with white Caucasians. We interpret that reduced Wnt signaling could contribute to impaired insulin signaling in South Asians.

show abstract

Section: Discussionmentioning

confidence: 58%

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Also shown in other literatures, acidosis was reported to enhance osteoclast formation in cats (Muzylak, Arnett, Price, & Horton, ) and regulates survival of mature rat osteoclast (Pereverzev et al, ; Yuan et al, ). Additionally, the elevated expression of sclerostin ( Sost ) would have also induced Trap5b expression via the RANKL‐dependent pathway for bone remodelling and resorption (Weivoda, Youssef, & Oursler, ; Wijenayaka et al, ). Taken together, the phenotype presented by ch‐ch constructs had resembled chronic acidosis in physiology, which induced calcium efflux and cell‐mediated bone resorption (Gasser, Hulter, Imboden, & Krapf, ).…”

Section: Discussionmentioning

confidence: 99%

Recapitulating bone development events in a customised bioreactor through interplay of oxygen tension, medium pH, and systematic differentiation approaches

Lee

Hess

Friedrichs

et al. 2019

J Tissue Eng Regen Med

View full text Add to dashboard Cite

Bone development and homeostasis are intricate processes that require co‐existence and dynamic interactions among multiple cell types. However, controlled dynamic niches that derive and support stable propagation of these cells from single stem cell source is not sustainable in conventional culturing vessels. In bioreactor cultures that support dynamic niches, the limited source and stability of growth factors are often a major limiting factor for long‐term in vitro cultures. Hence, alternative growth factor‐free differentiation approaches are designed and their efficacy to achieve different osteochondral cell types is investigated. Briefly, a dynamic niche is achieved by varying medium pH, oxygen tension (pO2) distribution in bioreactor, initiating chondrogenic differentiation with chondroitin sulphate A (CSA), and implementing systematic differentiation regimes. In this study, we demonstrated that CSA is a potent chondrogenic inducer, specifically in combination with acidic medium and low pO2. Further, endochondral ossification is recapitulated through a systematic chondrogenic–osteogenic (ch‐os) differentiation regime, and multiple osteochondral cell types are derived. Chondrogenic hypertrophy was also enhanced specifically in high pO2 regions. Consequently, mineralised constructs with higher structural integrity, volume, and tailored dimensions are achieved. In contrast, a continuous osteogenic differentiation regime (os‐os) has derived compact and dense constructs, whereas a continuous chondrogenic differentiation regime (ch‐ch) has attenuated construct mineralisation and impaired development. In conclusion, a growth factor‐free differentiation approach is achieved through interplay of pO2, medium pH, and systematic differentiation regimes. The controlled dynamic niches have recapitulated endochondral ossification and can potentially be exploited to derive larger bone constructs with near physiological properties.

show abstract

“…Indeed, a number of studies indicates other organs such kidney, aorta and testes as producing sclerostin (23). algorithm is based on over 850 murine DNA sequences that were identified to bind the PPARG::RXRA heterodimer (Suppl.…”

Section: Pparg Transcription Factor Is Essential For Sclerostin Produmentioning

confidence: 99%

PPARG in osteocytes is essential for sclerostin expression, bone mass, marrow adiposity and TZD-induced bone loss

Baroi

Czernik

Chougule

et al. 2020

Preprint

View full text Add to dashboard Cite

PPARG role in regulation of osteocyte function is largely unknown. We report that PPARG is essential for sclerostin production, a recently approved target to treat osteoporosis. There is an excellent correlation in osteocytes between Sost/sclerostin and PPARG at the transcript and protein levels, and increased bone mass in mice with osteocyte-specific deletion of PPARG (γOTKO) correlated with increased WNT signaling and bone forming activity of endosteal osteoblasts and decreased marrow fat. The 8 kb sequence upstream of Sost gene transcription start site possesses multiple PPARG binding elements (PPREs) with at least two of them binding PPARG with dynamics reflecting its activation and the levels of Sost transcript and sclerostin protein expression. Older γOTKO female mice are largely protected from TZD-induced bone loss providing proof of concept that PPARG in osteocytes can be pharmacologically targeted. Our study opens the possibility to consider repurposing PPARG as a target for treatment of osteoporosis.

show abstract

Sclerostin expression and functions beyond the osteocyte

Cited by 111 publications

References 67 publications

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

Recapitulating bone development events in a customised bioreactor through interplay of oxygen tension, medium pH, and systematic differentiation approaches

PPARG in osteocytes is essential for sclerostin expression, bone mass, marrow adiposity and TZD-induced bone loss

Contact Info

Product

Resources

About