Robo2 promotes osteoblast differentiation and mineralization through autophagy and is activated by parathyroid hormone induction

Yuan, Ning; Wang, Xiaojuan; He, Ming-Hai

doi:10.1016/j.aanat.2023.152070

Cited by 3 publications

(3 citation statements)

References 21 publications

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“…Other notable proteins among the 37 positively associated with LAZ include insulin-like growth factor-1 (IGF-1) which acts in concert with growth hormone to control linear growth in children 46 and a Wnt inhibitor, secreted frizzled-related protein 4 (SFRP4), involved in formation of bone cortex 47 . The list also includes effectors of CNS development: e.g., RET which encodes the receptor tyrosine kinase for glial cell derived neurotrophic factor (GDNF) 48 ; the axon guidance protein SLIT and NTRK like family member 5 (SLITRK5) 49 , BDNF/NT-3 growth factors receptor (NTRK2) which is involved in synaptogenesis and learning and memory 50 , plus roundabout homolog 2 (ROBO2), an axon guidance receptor recently reported to also promote osteoblast differentiation and mineralization 51 (see Fig. 3b for complete list of these proteins and their functional annotations).…”

Section: Resultsmentioning

confidence: 99%

“…The list also includes effectors of CNS development: e.g., RET which encodes the receptor tyrosine kinase for glial cell derived neurotrophic factor (GDNF) 48 ; the axon guidance protein SLIT and NTRK like family member 5 (SLITRK5) 49 , BDNF/NT-3 growth factors receptor (NTRK2) which is involved in synaptogenesis and learning and memory 50 , plus roundabout homolog 2 (ROBO2), an axon guidance receptor recently reported to also promote osteoblast differentiation and mineralization 51 (see Fig. 3b for complete list of these proteins and their functional annotations).…”

Section: Effects Of Mdcf-2 On the Plasma Proteomementioning

confidence: 99%

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A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth

Mostafa,

Hibberd,

Hartman

et al. 2024

Preprint

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Background Globally, stunting affects ~150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches. Methods 124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled genomes (MAGs) in serially collected fecal samples and levels of growth-associated proteins were measured in plasma. Findings Children who had received MDCF-2 were significantly less stunted during follow-up than those who received a standard ready-to-use supplementary food (RUSF) [linear mixed-effects model, βtreatment group x study week (95% CI) = 0.002 (0.001, 0.003); P=0.004]. They also had elevated fecal abundances of Agathobacter faecis, Blautia massiliensis, Lachnospira and Dialister, plus increased levels of a group of 37 plasma proteins (linear model; FDR-adjusted P<0.1), including IGF-1, neurotrophin receptor NTRK2 and multiple proteins linked to musculoskeletal and CNS development, that persisted for 6-months post-intervention. Interpretation MDCF-2 treatment of Bangladeshi children with MAM, which produced significant improvements in wasting during intervention, also reduced stunting during follow-up. These results suggest that the effectiveness of supplementary foods for undernutrition may be improved by including ingredients that sponsor healthy microbiota-host co-development.

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Section: Resultsmentioning

confidence: 99%

Section: Effects Of Mdcf-2 On the Plasma Proteomementioning

confidence: 99%

A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth

Mostafa,

Hibberd,

Hartman

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Other notable proteins among the 37 positively associated with LAZ include insulin-like growth factor-1 (IGF-1) which acts in concert with growth hormone to control linear growth in children 46 and a Wnt inhibitor, secreted frizzled-related protein 4 (SFRP4), involved in formation of bone cortex. 47 The list also includes effectors of CNS development: e.g., RET which encodes the receptor tyrosine kinase for glial cell derived neurotrophic factor (GDNF) 48 ; the axon guidance protein SLIT and NTRK like family member 5 (SLITRK5), 49 BDNF/NT-3 growth factors receptor (NTRK2) which is involved in synaptogenesis and learning and memory, 50 plus roundabout homolog 2 (ROBO2), an axon guidance receptor recently reported to also promote osteoblast differentiation and mineralization 51 (see Fig. 3 b for complete list of these proteins and their functional annotations).…”

Section: Resultsmentioning

confidence: 99%

A microbiota-directed complementary food intervention in 12–18-month-old Bangladeshi children improves linear growth

Mostafa,

Hibberd,

Hartman

et al. 2024

eBioMedicine

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IMPC-based screening revealed that ROBO1 can regulate osteoporosis by inhibiting osteogenic differentiation

Zhang,

Wang,

Zheng

et al. 2024

Front. Cell Dev. Biol.

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IntroductionThe utilization of denosumab in treating osteoporosis highlights promising prospects for osteoporosis intervention guided by gene targets. While omics-based research into osteoporosis pathogenesis yields a plethora of potential gene targets for clinical transformation, identifying effective gene targets has posed challenges.MethodsWe first queried the omics data of osteoporosis clinical samples on PubMed, used International Mouse Phenotyping Consortium (IMPC) to screen differentially expressed genes, and conducted preliminary functional verification of candidate genes in human Saos2 cells through osteogenic differentiation and mineralization experiments. We then selected the candidate genes with the most significant effects on osteogenic differentiation and further verified the osteogenic differentiation and mineralization functions in mouse 3T3-E1 and bone marrow mesenchymal stem cells (BMSC). Finally, we used RNA-seq to explore the regulation of osteogenesis by the target gene.ResultsWe identified PPP2R2A, RRBP1, HSPB6, SLC22A15, ADAMTS4, ATP8B1, CTNNB1, ROBO1, and EFR3B, which may contribute to osteoporosis. ROBO1 was the most significant regulator of osteogenesis in both human and mouse osteoblast. The inhibitory effect of Robo1 knockdown on osteogenic differentiation may be related to the activation of inflammatory signaling pathways.ConclusionOur study provides several novel molecular mechanisms involved in the pathogenesis of osteoporosis. ROBO1 is a potential target for osteoporosis intervention.

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Robo2 promotes osteoblast differentiation and mineralization through autophagy and is activated by parathyroid hormone induction

Cited by 3 publications

References 21 publications

A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth

A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth

A microbiota-directed complementary food intervention in 12–18-month-old Bangladeshi children improves linear growth

IMPC-based screening revealed that ROBO1 can regulate osteoporosis by inhibiting osteogenic differentiation

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