Hydrogen sulfide is a novel regulator implicated in glucocorticoids-inhibited bone formation

Ma, Jiguang; Shi, Changgui; Liu, Zhongyang; Han, Bin; Guo, Lei; Zhu, Lei; Ye, Tianwen

doi:10.18632/aging.102269

Cited by 25 publications

(24 citation statements)

References 51 publications

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“…In this regard, the clinical similarities between bone damage in glucocorticoid-induced osteoporosis and T2D-related bone involvement seem to find some biological confirmation. Indeed, very recent data show that in rats, dexamethasone decreases serum H2S and two key H2S-generating enzymes in the bone marrow and the H2S treatment significantly relieved the inhibitory effect of dexamethasone on bone formation [162]. Therefore, it is possible to hypothesize that the reduced H2S levels in T2DM may depend on the increased cortisol levels at least in some diabetic patients.…”

Section: Journal Of Diabetes Researchmentioning

confidence: 99%

Pathophysiology and Management of Type 2 Diabetes Mellitus Bone Fragility

Eller-Vainicher

Cairoli

Grassi

et al. 2020

Journal of Diabetes Research

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Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of bone fragility fractures compared to nondiabetic subjects. This increased fracture risk may occur despite normal or even increased values of bone mineral density (BMD), and poor bone quality is suggested to contribute to skeletal fragility in this population. These concepts explain why the only evaluation of BMD could not be considered an adequate tool for evaluating the risk of fracture in the individual T2DM patient. Unfortunately, nowadays, the bone quality could not be reliably evaluated in the routine clinical practice. On the other hand, getting further insight on the pathogenesis of T2DM-related bone fragility could consent to ameliorate both the detection of the patients at risk for fracture and their appropriate treatment. The pathophysiological mechanisms underlying the increased risk of fragility fractures in a T2DM population are complex. Indeed, in T2DM, bone health is negatively affected by several factors, such as inflammatory cytokines, muscle-derived hormones, incretins, hydrogen sulfide (H2S) production and cortisol secretion, peripheral activation, and sensitivity. All these factors may alter bone formation and resorption, collagen formation, and bone marrow adiposity, ultimately leading to reduced bone strength. Additional factors such as hypoglycemia and the consequent increased propensity for falls and the direct effects on bone and mineral metabolism of certain antidiabetic medications may contribute to the increased fracture risk in this population. The purpose of this review is to summarize the literature evidence that faces the pathophysiological mechanisms underlying bone fragility in T2DM patients.

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Section: Journal Of Diabetes Researchmentioning

confidence: 99%

Pathophysiology and Management of Type 2 Diabetes Mellitus Bone Fragility

Eller-Vainicher

Cairoli

Grassi

et al. 2020

Journal of Diabetes Research

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“…Bone metabolism maintains bone mass by balancing bone resorption and formation 31‐34 . As a highly selective calcium channel in the TRPV subfamily, TRPV6 is an important protein in osteoclasts and participates in the regulation of osteoclast differentiation and bone resorption 18 .…”

Section: Discussionmentioning

confidence: 99%

The calcium channel TRPV6 is a novel regulator of RANKL‐induced osteoclastic differentiation and bone absorption activity through the IGF–PI3K–AKT pathway

Zhu

Zhou

et al. 2020

Cell Proliferation

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Objectives Calcium ion signals are important for osteoclast differentiation. Transient receptor potential vanilloid 6 (TRPV6) is a regulator of bone homeostasis. However, it was unclear whether TRPV6 was involved in osteoclast formation. Therefore, the aim of this study was to evaluate the role of TPRV6 in bone metabolism and to clarify its regulatory role in osteoclasts at the cellular level. Materials and methods Bone structure and histological changes in Trpv6 knockout mice were examined using micro‐computed tomography and histological analyses. To investigate the effects of Trpv6 on osteoclast function, we silenced or overexpressed Trpv6 in osteoclasts via lentivirus transfection, respectively. Osteoclast differentiation and bone resorption viability were measured by tartrate‐resistant acid phosphatase (TRAP) staining and pit formation assays. The expression of osteoclast marker genes, including cathepsin k, DC‐STAMP, Atp6v0d2 and TRAP, was measured by qRT‐PCR. Cell immunofluorescence and Western blotting were applied to explore the mechanisms by which the IGF‐PI3K‐AKT pathway was involved in the regulation of osteoclast formation and bone resorption by Trpv6. Results We found that knockout of Trpv6 induced osteoporosis and enhanced bone resorption in mice, but did not affect bone formation. Further studies showed that Trpv6, which was distributed on the cell membrane of osteoclasts, acted as a negative regulator for osteoclast differentiation and function. Mechanistically, Trpv6 suppressed osteoclastogenesis by decreasing the ratios of phosphoprotein/total protein in the IGF–PI3K–AKT signalling pathway. Blocking of the IGF–PI3K–AKT pathway significantly alleviated the inhibitory effect of Trpv6 on osteoclasts formation. Conclusions Our study confirmed the important role of Trpv6 in bone metabolism and clarified its regulatory role in osteoclasts at the cellular level. Taken together, this study may inspire a new strategy for the treatment of osteoporosis.

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“…resorption and formation [28][29][30][31] . As a highly selective calcium channel in the TRPV subfamily, TRPV6 is an important protein in osteoclasts and participates in the regulation of osteoclast differentiation and bone resorption [16] .…”

Section: Bone Metabolism Maintains Bone Mass Through Complex Regulatimentioning

confidence: 99%

Calcium Channel TRPV6 is a Novel Regulator in RANKL-induced Osteoclastic Differentiation and Activity through the IGF–PI3K–AKT Pathway

Ma¹,

Zhu²,

Zhou³

et al. 2020

Preprint

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Background: Calcium ion signals are important for osteoclast differentiation. Transient receptor potential vanilloid 6 (TRPV6) is a novel regulator of bone homeostasis. However, it is unclear whether TRPV6 was involved in the process of osteoclast formation.Results: In the present study, we found that knockout of the TRPV6 gene induced osteoporosis in mice, and depletion of TRPV6 did not affect bone formation but significantly enhanced bone resorption. Further studies showed that TRPV6, distributed on the cell membrane of osteoclasts, was a negative regulator of osteoclast differentiation and function. Mechanistically, TRPV6 suppressed osteoclastogenesis by decreasing the production the IGF1R and AKT ligands to inhibit the IGF–PI3K–AKT signaling pathway. Blocking the IGF–PI3K–AKT pathway significantly reduced the effect of TRPV6 on osteoclasts.Conclusion: Our study confirmed the important role of TPRV6 in bone metabolism and clarified its regulatory role on osteoclasts at the cellular level, which may provide a new strategy for the treatment of osteoporosis.

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Hydrogen sulfide is a novel regulator implicated in glucocorticoids-inhibited bone formation

Cited by 25 publications

References 51 publications

Pathophysiology and Management of Type 2 Diabetes Mellitus Bone Fragility

Pathophysiology and Management of Type 2 Diabetes Mellitus Bone Fragility

The calcium channel TRPV6 is a novel regulator of RANKL‐induced osteoclastic differentiation and bone absorption activity through the IGF–PI3K–AKT pathway

Calcium Channel TRPV6 is a Novel Regulator in RANKL-induced Osteoclastic Differentiation and Activity through the IGF–PI3K–AKT Pathway

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