Connecting Bone and Fat: the Potential Role for Sclerostin

Fairfield, Heather; Rosen, Clifford J.; Reagan, Michaela R.

doi:10.1007/s40610-017-0057-7

Cited by 37 publications

(26 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As described above, SOST has emerged as an endocrine factor that regulates glucose and fat metabolism . Outside of the skeleton, SOST is present in the serum, supporting a circulating endocrine role . Circulating SOST increases progressively with age and the higher serum SOST levels found in elderly postmenopasual women are associated with a greater risk of hip fractures .…”

Section: Wnt Signaling In Aging Adipose Tissuementioning

confidence: 94%

“…71 Outside of the skeleton, SOST is present in the serum, supporting a circulating endocrine role. 155,156 Circulating SOST increases progressively with age and the higher serum SOST levels found in elderly postmenopasual women are associated with a greater risk of hip fractures. [157][158][159] More recently, circulating SOST has been reported to be associated with glucose and adipose tissue metabolism.…”

Section: Wnt Signaling In Aging Adipose Tissuementioning

confidence: 99%

See 1 more Smart Citation

Wnt signaling in bone, kidney, intestine, and adipose tissue and interorgan interaction in aging

Chen

Xie

Shu

et al. 2018

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Over the last two decades, it has become increasingly apparent that Wnt signaling plays a critical role in development and adult tissue homeostasis in multiple organs and in the pathogenesis of many diseases. In particular, a crucial role for Wnt signaling in bone development and bone tissue homeostasis has been well recognized. Numerous genome-wide association studies confirmed the importance of Wnt signaling in controlling bone mass. Moreover, ample evidence suggests that Wnt signaling is essential for kidney, intestine, and adipose tissue development and homeostasis. Recent emerging evidence demonstrates that Wnt signaling may play a fundamental role in the aging process of those organs. New discoveries show that bone is not only the major reservoir for calcium and phosphate storage, but also the largest organ with multiple functions, including mineral and energy metabolism. The interactions among bone, kidney, intestine, and adipose tissue are controlled and regulated by several endocrine signals, including FGF23, klotho, sclerostin, osteocalcin, vitamin D, and leptin. Since the aging process is characterized by structural and functional decline in almost all tissues and organs, understanding the Wnt signaling-related interactions among bone, kidney, intestine, and adipose tissue in aging may shed light on the pathogenesis of age-related diseases.

show abstract

Section: Wnt Signaling In Aging Adipose Tissuementioning

confidence: 94%

Section: Wnt Signaling In Aging Adipose Tissuementioning

confidence: 99%

Wnt signaling in bone, kidney, intestine, and adipose tissue and interorgan interaction in aging

Chen

Xie

Shu

et al. 2018

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

show abstract

“…Overall, there are a multitude of ways in which MAT and BMAs may contribute to tumor growth, and clinically targeting MAT is an interesting and innovative concept. It is possible that therapies that build bone may also inhibit MAT, as we have recently demonstrated with anti-sclerostin antibodies [54,57], and as others have found with PTH [47] and leptin [69]. The FGF family members may also hold promise for targeting to modulate not only bone, but also MAT.…”

Section: Discussionmentioning

confidence: 92%

“…Many researchers have speculated that MAT impedes bone development due to direct effects on mature osteoblasts or MSCs, but direct evidence is lacking due to the challenges of specifically modulating MAT. Interestingly, many of the signaling pathways in MSCs that induce osteogenic differentiation inhibit adipogenic differentiation, such as Wnt [54,57] and parathyroid hormone (PTH) signaling [47,58]. Thus, increased adipogenesis may decrease the pool of progenitor cells able to undergo osteogenesis, which would decrease the number of osteoblasts in the niche and likely decrease bone volume fractions in cortical and trabecular bone regions.…”

Section: Adipocyte and Adipokine Effects On Other Cells In The Tummentioning

confidence: 99%

Reflections on Cancer in the Bone Marrow: Adverse Roles of Adipocytes

2017

Self Cite

View full text Add to dashboard Cite

This review highlights the recent advances in our understanding of adipocyte contributions to carcinogenesis or cancer disease progression for cancers in the bone. Purpose In this review, we aim to describe bone marrow adipose tissue and discuss the soluble adipocyte-derived cytokines (adipokines) or endocrine factors, adipocyte-derived lipids, and the actual or putative juxtacrine signaling between bone marrow adipocytes and tumor cells in the bone marrow. This relationship likely affects tumor cell initiation, proliferation, metastasis, and/or drug resistance. Recent Findings Bone marrow adipose may affect tumor proliferation, drug resistance, or cancer-induced bone disease and hence may be a new target in the fight against cancer. Summary Overall, evidence is mixed regarding the role of bone marrow adipose and adipocytes in cancer progression, and more research in this arena is necessary to determine how these bone marrow microenvironmental cells contribute to malignancies in the marrow to identify novel, potentially targetable pathways.

show abstract

“…Pereira RC, et al suggests that the increase in osteocyte sclerostin expression in KT patients may be related to the use of immune-suppressive medications probably contributing to bone loss observed in these patients [ 10 ]. Sclerostin is traditionally characterized as inhibitor of osteoblastogenesis (Wnt pathway) is being investigated for new roles in adipocytes development and bone marrow maintenance [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

The effect of vitamin D and zoledronic acid in bone marrow adiposity in kidney transplant patients: A post hoc analysis

et al. 2018

View full text Add to dashboard Cite

PurposeOsteoblasts and adipocytes are derived from mesenchymal stem cells. An imbalance in the differentiation of these lineages could affect the preservation of bone integrity. Several studies have suggested the importance of this imbalance in the pathogenesis of osteoporosis after kidney transplant (KT), but the role of bone marrow adiposity in this process is not well known, and if the treatment with the anti-absorptive (zoledronic acid-ZA) drugs could attenuate bone loss. Thus, our objective was compare bone marrow adiposity, osteoblasts and osteocytes before and after KT, verify an association between bone remodeling process (Turnover, Volume, and Mineralization—TMV classification), the osteocyte sclerostin expression to evaluate if there is a role of Wnt pathway, as well as the effect of ZA on these cells.MethodsWe studied 29 new living-donor KT patients. One group received ZA at the time of KT plus cholecalciferol for twelve months, and the other group received only cholecalciferol. Bone biopsies were performed at baseline and after 12 months of treatment. Histomorphometric evaluation was performed in bone and bone marrow adipocytes. Sclerostin (Scl) expression in osteocytes was evaluated by immunohistochemistry.ResultsSome bone marrow adiposity parameters were increased before KT. After KT, some of them remained increased and they worsened with the use of ZA. In the baseline, lower bone Volume and Turnover, were associated with increased bone marrow adiposity parameters (some of them). After KT, both groups showed the same associations. Osteocyte Scl expression after KT decreased with the use of ZA. We observed also an inverse association between bone adiposity parameters and lower osteocyte sclerostin expression 12 months after KT.ConclusionIn conclusion, the present study suggests that KT fails to normalize bone marrow adiposity, and it even gets worse with the use of ZA. Moreover, bone marrow adiposity is inversely associated with bone Volume and Turnover, which seems to be accentuated by the antiresorptive therapy.

show abstract

Connecting Bone and Fat: the Potential Role for Sclerostin

Cited by 37 publications

References 66 publications

Wnt signaling in bone, kidney, intestine, and adipose tissue and interorgan interaction in aging

Wnt signaling in bone, kidney, intestine, and adipose tissue and interorgan interaction in aging

Reflections on Cancer in the Bone Marrow: Adverse Roles of Adipocytes

The effect of vitamin D and zoledronic acid in bone marrow adiposity in kidney transplant patients: A post hoc analysis

Contact Info

Product

Resources

About