Galectin-3 is essential for proper bone cell differentiation and activity, bone remodeling and biomechanical competence in mice

Iacobini, Carla; Fantauzzi, Claudia Blasetti; Bedini, Rossella; Pecci, Raffaella; Bartolazzi, Armando; Amadio, Bruno; Pesce, Carlo; Pugliese, Giuseppe; Menini, Stefano

doi:10.1016/j.metabol.2018.02.001

Cited by 28 publications

(31 citation statements)

References 44 publications

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“…1,8 Gal-3 participates in bone homeostasis and regulates bone cell interactions. [15][16][17][18][19] Both Gal-3 and Runx2 protein levels increased in PD and DM compared with NC in the current work, and decreased in DMPD compared with DM in alveolar bone in our animal models. The increased Gal-3 was associated with enhanced periodontal bone mass in DM, whereas decreased Gal-3, potentially arising from decompensation of bone tissues, was associated with accelerated bone destruction in DMPD.…”

Section: Discussionmentioning

confidence: 78%

“…In addition, IL-6 is a common marker in PD with or without DM, and studies of inflammation have shown that IL-6 is a downstream factor from Gal-3. 17,48 Therefore, we detect the expression of IL-6, a mainly used marker in PD with or without DM, to figure out the inflammatory state of bone in the present study. Both osteoblasts and osteocytes expressed IL-6, which was notably decreased in DM and DMPD compared with NC in osteocytes.…”

Section: Discussionmentioning

confidence: 99%

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miR‐124‐3p increases in high glucose induced osteocyte‐derived exosomes and regulates galectin‐3 expression: A possible mechanism in bone remodeling alteration in diabetic periodontitis

Guo

Chen

et al. 2020

The FASEB Journal

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

miR‐124‐3p increases in high glucose induced osteocyte‐derived exosomes and regulates galectin‐3 expression: A possible mechanism in bone remodeling alteration in diabetic periodontitis

Guo

Chen

et al. 2020

The FASEB Journal

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“…This would reduce the ability of androgen to support bone mass accrual during puberty [40]. Altered sex-hormone regulation in the Lgals3-KO mother, during fetal development, might also explain why a different skeletal phenotype (increased age-related bone loss) has been reported when comparing Lgals3-KO mice to litters of background matched wildtype-mice [41]. More studies looking at systemic changes in hormones and growth factors in Lgals3-KO and Lgals3-R200S mice would help answer this question.…”

Section: Discussionmentioning

confidence: 99%

Mutation of the Galectin-3 Glycan Binding Domain (Lgals3-R200S) Enhances Cortical Bone Expansion in Male and Trabecular Bone Mass in Female Mice

Maupin

Dick

Vivarium³

et al. 2020

Preprint

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The study of galectin-3 is complicated by its ability to function both intracellularly and extracellularly. While the mechanism of galectin-3 secretion is unclear, studies have shown that the mutation of a highly conserved arginine to a serine in human galectin-3 (LGALS3-R186S) blocks glycan binding and secretion. To gain insight into the roles of extracellular and intracellular functions of galectin-3, we generated mice with the equivalent mutation (Lgals3-R200S) using CRISPR/Cas9-directed homologous recombination. Consistent with a reduction in galectin-3 secretion, we observed significantly reduced galectin-3 protein levels in the plasma of heterozygous and homozygous mutant mice. We observed a similar increased bone mass phenotype in Lgals3-R200S mutant mice at 36 weeks as we previously observed in Lgals3-KO mice with slight variation. Like Lgals3-KO mice, Lgals3-R200S females, but not males, had significantly increased trabecular bone mass. However, only male Lgals3-R200S mice showed increased cortical bone expansion, which we had previously observed in both male and female Lgals3-KO mice and only in female mice using a separate Lgals3 null allele (Lgals3). These results suggest that the trabecular bone phenotype of Lgals3-KO mice was driven primarily by loss of extracellular galectin-3. However, the cortical bone phenotype of Lgals3-KO mice may have also been influenced by loss of intracellular galectin-3. Future analyses of these mice will aid in identifying the cellular and molecular mechanisms that contribute to the Lgals3-deficient bone phenotype as well as aid in distinguishing the extracellular vs.intracellular roles of galectin-3 in various signaling pathways.

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“…Gal-3 KO mice are predisposed to OA ( 6 ), potentially due to the protective role that galectin-3 plays in chondrocyte survival ( 5 , 6 ). Galectin-3 KO mice also demonstrate decreased bone formation, increased bone resorption, accelerated trabecular bone loss and reduced bone strength as compared to wild-type mice, suggesting an important role for galectin-3 in bone remodeling and biomechanics ( 25 ). On the other hand, exogenous intra-articular galectin-3 administration promoted the development of arthritis in mice ( 19 ), and inhibition of galectin-3 through lentiviral-mediated delivery of galectin-3 shRNA ameliorated collagen-induced arthritis in rats ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

“…Investigation of in vitro signaling pathways in human OA chondrocytes revealed that both galectins-1 and-3 promote an inflammatory gene signature, at least in part through their role as upstream NF-κB signaling effectors ( 21 , 24 ). On the other hand, galectin-3 KO mice demonstrate increased cartilage damage in a mono-iodoacetate injection model of OA ( 6 ), and galectin-3 KO mice also demonstrate increased bone resorption and accelerated trabecular bone loss as compared to wild-type mice ( 25 ), suggesting a protective role for galectin-3 in OA.…”

Section: Introductionmentioning

confidence: 99%

Galectins-1 and-3 Increase in Equine Post-traumatic Osteoarthritis

et al. 2018

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Galectins are potent regulators of cell adhesion, growth and apoptosis in diverse cell types, including chondrocytes and synovial fibroblasts. Elevations in synovial fluid galectin-3 have been observed in rheumatoid arthritis, juvenile idiopathic arthritis and experimental inflammatory arthritis in animal models, whereas galectin-1 is thought to be protective. Less is known about galectins-1 and-3 in osteoarthritis (OA). Therefore, the purpose of this study was: (1) to determine whether galectin-1 and-3 synovial fluid concentrations and synovial membrane and cartilage histochemical staining were altered following osteochondral injury in an experimental equine osteoarthritis (OA) model and (2) to measure galectin-1 and-3 mRNA expression and synovial fluid concentrations in naturally occurring equine carpal OA. Synovial fluid galectin-1 and-3 concentrations were quantified using custom ELISAs in two research horse cohorts undergoing experimental OA induction (n = 5 and 4) and in a cohort of horses with naturally occurring carpal OA (n = 57). Galectin mRNA expression in synovial membrane and cartilage tissue obtained from carpal joints of horses with naturally occurring OA was measured using RT-qPCR, and galectin immunostaining was assessed in synovial membrane and osteochondral tissues in the experimental model (n = 5). Synovial fluid galectin-1 and-3 concentrations increased following experimental carpal osteochondral fragmentation. Cartilage galectin-1 mRNA expression increased with OA severity in naturally occurring disease. The superficial zone of healthy articular cartilage stained intensely for galectin-3 in sham-operated joints, whereas galectin-1 staining was nearly absent. Chondrocyte galectin-1 and-3 immunoreactivity increased following cartilage injury, particularly in galectin-1 positive chondrones. Galectins-1 and-3 are present in healthy equine synovial fluid and increase following post-traumatic OA. Healthy superficial zone chondrocytes express galectin-3, whereas galectin-1 chondrocyte staining is limited predominantly to chondrones and injured cartilage. Further work is needed to clarify the functions of galectins-1 and-3 in healthy and OA joints.

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Galectin-3 is essential for proper bone cell differentiation and activity, bone remodeling and biomechanical competence in mice

Cited by 28 publications

References 44 publications

miR‐124‐3p increases in high glucose induced osteocyte‐derived exosomes and regulates galectin‐3 expression: A possible mechanism in bone remodeling alteration in diabetic periodontitis

miR‐124‐3p increases in high glucose induced osteocyte‐derived exosomes and regulates galectin‐3 expression: A possible mechanism in bone remodeling alteration in diabetic periodontitis

Mutation of the Galectin-3 Glycan Binding Domain (Lgals3-R200S) Enhances Cortical Bone Expansion in Male and Trabecular Bone Mass in Female Mice

Galectins-1 and-3 Increase in Equine Post-traumatic Osteoarthritis

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