Thy-1 (CD90) promotes bone formation and protects against obesity

Objectives: Fluorine, an organic trace element, has been shown to unfavourably effect osteoclasts function at a low dose. Use of hydroxyapatite (HA) has been effective in exploring its roles in promoting bone repair. In this study, we used HA modified with fluorine to investigate whether it could influence osteoclastic activity in vitro and ovariectomy-induced osteoclasts hyperfunction in vivo. Materials and methods: Fluorohydroxyapatite (FHA) was obtained and characterized by scanning electron microscope (SEM). Osteoclasts proliferation and apoptosis treated with FHA were assessed by MTT and TUNEL assay. SEM, F-actin, TRAP activity and bone resorption experiment were performed to determine the influence of FHA on osteoclasts differentiation and function. Moreover, HA and FHA were implanted into ovariectomized osteoporotic and sham surgery rats. Histology and Micro-CT were examined for further verification. Results: Fluorine released from FHA slowly and sustainably. FHA hampered osteoclasts proliferation, promoted osteoclasts apoptosis, suppressed osteoclasts differentiation and function. Experiments in vivo validated that FHA participation brought about an inhibitory effect on osteoclasts hyperfunction and less bone absorption. Conclusion:The results indicated that FHA served as an efficient regulator to attenuate osteoclasts formation and function and was proposed as a candidature for bone tissue engineering applications.

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“…23 They are always characterized by increased osteoclasts formation. 23 They are always characterized by increased osteoclasts formation.…”

Section: Discussionmentioning

confidence: 99%

Fluorine‐contained hydroxyapatite suppresses bone resorption through inhibiting osteoclasts differentiation and function in vitro and in vivo

et al. 2019

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“…Substantial regeneration of the diaphysis and the epiphyseal plate was only observed upon transplantation of Thy-1-positive periosteumderived cells compared with controls without cells or unsorted periosteum-derived cells (86). Accordingly, Thy-1-positive dental pulp cells localized in the subodontoblastic layer had a greater ability to differentiate into hard tissue-forming cells compared with Thy-1negative cells (87 Consistently, MSCs isolated from Thy-1-deficient mice showed a decreased potential to differentiate into osteoblasts compared with MSCs from WT mice as shown by diminished ALP activity and mineralization capacity as well as reduced expression of the master transcription factor of osteogenic differentiation Runx2 and its target genes osteocalcin, osterix, and tissue nonspecific alkaline phosphatase 1 (32). Blocking the interaction of Thy-1 with integrin b3 signaling reduced the osteogenic differentiation of MSCs (32).…”

Section: Thy-1 Controls the Osteogenic Differentiation Of Mscs And Bomentioning

confidence: 96%

“…Accordingly, Thy-1-positive dental pulp cells localized in the subodontoblastic layer had a greater ability to differentiate into hard tissue-forming cells compared with Thy-1negative cells (87 Consistently, MSCs isolated from Thy-1-deficient mice showed a decreased potential to differentiate into osteoblasts compared with MSCs from WT mice as shown by diminished ALP activity and mineralization capacity as well as reduced expression of the master transcription factor of osteogenic differentiation Runx2 and its target genes osteocalcin, osterix, and tissue nonspecific alkaline phosphatase 1 (32). Blocking the interaction of Thy-1 with integrin b3 signaling reduced the osteogenic differentiation of MSCs (32). Moreover, seeding Thy-1-deficient MSCs on recombinant immobilized Thy-1 compensated for the lack of Thy-1 and resulted in an osteogenic differentiation similar to that of WT MSCs.…”

Section: Thy-1 Controls the Osteogenic Differentiation Of Mscs And Bomentioning

confidence: 96%

“…Obviously, the high expression of Thy-1, its localization in lipid rafts, and high carbohydrate content allow its interaction with different receptors, which results in the control of their activity. By acting in cis or trans, Thy-1 is able to interfere with several signaling pathways, including Smad, wingless-type mouse mammary tumor virus integration site (Wnt), Src, notch, and peroxisome proliferator-activated receptor g (Pparg) (22,26,27,(29)(30)(31)(32)(33)(34).…”

Section: Structure Of Thy-1 and Signaling Cascadesmentioning

confidence: 99%

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Thy‐1: more than a marker for mesenchymal stromal cells

Saalbach

Anderegg

2019

FASEB j.

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Balanced differentiation of mesenchymal stromal cells (MSCs) into osteoblasts and adipocytes is essential for healthy bone and fat homeostasis. A disturbed balance of MSC differentiation results in bone loss and increased adipogenesis as observed in several human conditions, such as osteoporosis, obesity, and aging. This reflects the importance of MSC fate decision. Therefore, it is important to identify factors that regulate the balance between osteogenic and adipogenic differentiation of MSCs so as to identify new targets to improve bone formation in osteoporosis and control adipose tissue development. There is accumulating evidence that thymus cell antigen 1 (Thy‐1), also known as CD90, expressed on MSCs, plays a critical role in the fate decision of MSCs. Recently, Thy‐1 has been shown to promote osteogenic differentiation of MSCs and thus bone formation while inhibiting adipogenic differentiation and restricting adipose tissue accumulation. The clinical importance of these findings was validated by the detection of reduced serum soluble Thy‐1 in patients with disturbed bone remodeling. In this review, we aim to summarize data on the impact of Thy‐1 on the control of MSC differentiation and its consequences for bone and fat formation.—Saalbach, A., Anderegg, U. Thy‐1: more than a marker for mesenchymal stromal cells. FASEB J. 33, 6689–6696 (2019). http://www.fasebj.org

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“…In particular, adipo-osteogenic balance is reciprocally maintained. 5,6 Recently, the regulation of differentiation by several lipid species has been suggested as an important differentiation control mechanism. 2 Dysregulation of this balance is linked to pathophysiologic states.…”

Section: Introductionmentioning

confidence: 99%

Glucosylceramide synthase regulates adipo‐osteogenic differentiation through synergistic activation of PPARγ with GlcCer

et al. 2019

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Abbreviations: A/B, N-terminal regulatory domain; AIM, adipogenic induction medium; ALP, alkaline phosphatase; AMP-DNM, N-(5-adamantane-1-ylmethoxy-pentyl)-deoxynojirimycin; aP2, adipocyte protein 2; ATF2, activating transcription factor 2; BMP2, bone morphogenetic protein 2; BV, bone volume; C/EBPα, CCAAT-enhancer binding protein α AbstractDysregulation of the adipo-osteogenic differentiation balance of mesenchymal stem cells (MSCs), which are common progenitor cells of adipocytes and osteoblasts, has been associated with many pathophysiologic diseases, such as obesity, osteopenia, and osteoporosis. Growing evidence suggests that lipid metabolism is crucial for maintaining stem cell homeostasis and cell differentiation; however, the detailed underlying mechanisms are largely unknown. Here, we demonstrate that glucosylceramide (GlcCer) and its synthase, glucosylceramide synthase (GCS), are key determinants of MSC differentiation into adipocytes or osteoblasts. GCS expression was increased during adipogenesis and decreased during osteogenesis. Targeting GCS using RNA interference or a chemical inhibitor enhanced osteogenesis and inhibited adipogenesis by controlling the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ). Treatment with GlcCer sufficiently rescued adipogenesis and inhibited osteogenesis in GCS knockdown MSCs. Mechanistically, GlcCer interacted directly with PPARγ through A/B domain and synergistically enhanced rosiglitazone-induced PPARγ activation without changing PPARγ expression, thereby treatment with exogenous GlcCer increased adipogenesis and inhibited osteogenesis. Animal studies demonstrated that inhibiting GCS reduced adipocyte formation in white adipose tissues under normal chow diet and high-fat diet feeding and accelerated bone repair in a calvarial defect model. Taken together, our findings identify a novel lipid metabolic regulator for the control of MSC differentiation and may have important therapeutic implications.

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Thy-1 (CD90) promotes bone formation and protects against obesity

Cited by 86 publications

References 64 publications

Fluorine‐contained hydroxyapatite suppresses bone resorption through inhibiting osteoclasts differentiation and function in vitro and in vivo

Fluorine‐contained hydroxyapatite suppresses bone resorption through inhibiting osteoclasts differentiation and function in vitro and in vivo

Thy‐1: more than a marker for mesenchymal stromal cells

Glucosylceramide synthase regulates adipo‐osteogenic differentiation through synergistic activation of PPARγ with GlcCer

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