Honors & Awards
Best Paper Award for Associate Member of Annual Congress of Hong Kong Orthopaedic Association, Hong Kong Orthopaedic Association (2016)
Best Paper Award of International Congress of Chinese Orthopaedic Association, Chinese Orthopaedic Association (2012)
National Scholarship for Postgraduates, Ministry of Education of the People’s Republic of China (2012)
Doctor of Philosophy, Chinese University of Hong Kong (2017)
Master of Science, Shanghai Jiaotong University (2014)
Bachelor of Science, Shandong University (2009)
- Modulation of the Inflammatory Response and Bone Healing FRONTIERS IN ENDOCRINOLOGY 2020; 11
IL-4 Overexpressing Mesenchymal Stem Cells within Gelatin-Based Microribbon Hydrogels Enhance Bone Healing in a Murine Long Bone Critical-size Defect Model.
Journal of biomedical materials research. Part A
Mesenchymal stem cell (MSC)-based therapy is a promising strategy for bone repair. Furthermore, the innate immune system, and specifically macrophages, play a crucial role in the differentiation and activation of MSCs. The anti-inflammatory cytokine IL-4 converts pro-inflammatory M1 macrophages into a tissue regenerative M2 phenotype, which enhances MSC differentiation and function. We developed lentivirus-transduced IL-4 over-expressing MSCs (IL-4 MSCs) that continuously produce IL-4 and polarize macrophages toward an M2 phenotype. In the current study, we investigated the potential of IL-4 MSCs delivered using a macroporous gelatin-based microribbon (μRB) scaffold for healing of critical size long bone defects in Mice. IL-4 MSCs within μRBs enhanced M2 marker expression without inhibiting M1 marker expression in the early phase, and increased macrophage migration into the scaffold. Six weeks after establishing the bone defect, IL-4 MSCs within μRBs enhanced bone formation and helped bridge the long bone defect. IL-4 MSCs delivered using macroporous μRB scaffold is potentially a valuable strategy for the treatment of critical size long bone defects. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/jbm.a.36982
View details for PubMedID 32363683
TRAF3 modulates cartilage degradation through its suppression of interleukin 17 signaling.
The American journal of pathology
Interleukin 17A (IL-17A) plays critical role in the pathogenesis of autoimmune diseases through driving inflammatory cascades. However, the role of IL-17 in osteoarthritis (OA) is not well understood. TNF receptor associated factor 3 (TRAF3) is a receptor proximal negative regulator of IL-17 signaling. Whether TRAF3 exerts regulatory effects on catabolic and anabolic gene expression in chondrocytes and contributes to the pathogenesis of OA is not well understood. In this study, we found that TRAF3 notably suppressed IL-17-induced NF-κB and MAPK activation and subsequent the production of matrix-degrading enzymes. On the contrary, TRAF3 depletion enhanced IL-17 signaling, along with increased matrix-degrading enzymes production. In vivo, cartilage destruction caused by surgery-induced OA was markedly alleviated both in IL-17A deficient mice (IL17a-/-) and TRAF3 transgenic mice (T3TG). In contrast, silencing TRAF3 through adenoviruses worsened cartilage degradation in experimental OA. Moreover, the destructive effect of IL-17 on cartilage was abolished in T3TG mice in an IL-17 intra-articular (IA) injection animal model. Similarly, genetic deletion of IL-17 blocked TRAF3 knock down-mediated promotion of cartilage destruction, which suggests that the protective effect of TRAF3 on cartilage is mediated by its suppression of IL-17 signaling. Collectively, our results suggest that TRAF3 is critical in negative regulation of IL-17-mediated cartilage degradation and pathogenesis of OA, and may serve as a potential new therapy target for OA.
View details for DOI 10.1016/j.ajpath.2020.04.016
View details for PubMedID 32416098
Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility
2019; 12 (594)
The ability of skeletal muscle to switch between lipid and glucose oxidation for ATP production during metabolic stress is pivotal for maintaining systemic energy homeostasis, and dysregulation of this metabolic flexibility is a dominant cause of several metabolic disorders. However, the molecular mechanism that governs fuel selection in muscle is not well understood. Here, we report that brain-derived neurotrophic factor (BDNF) is a fasting-induced myokine that controls metabolic reprograming through the AMPK/CREB/PGC-1α pathway in female mice. Female mice with a muscle-specific deficiency in BDNF (MBKO mice) were unable to switch the predominant fuel source from carbohydrates to fatty acids during fasting, which reduced ATP production in muscle. Fasting-induced muscle atrophy was also compromised in female MBKO mice, likely a result of autophagy inhibition. These mutant mice displayed myofiber necrosis, weaker muscle strength, reduced locomotion, and muscle-specific insulin resistance. Together, our results show that muscle-derived BDNF facilitates metabolic adaption during nutrient scarcity in a gender-specific manner and that insufficient BDNF production in skeletal muscle promotes the development of metabolic myopathies and insulin resistance.
View details for DOI 10.1126/scisignal.aau1468
View details for Web of Science ID 000481406900002
View details for PubMedID 31409756
The relationship between sarcopenia and fragility fracturea systematic review
2019; 30 (3): 541–53
Sarcopenia is a common geriatric syndrome characterized by progressive decrease of muscle mass and function leading to an increased risk of physical disability, poor quality of life, and mortality. Increasing evidence shows that sarcopenia is related with fragility fractures. This systematic review aimed to summarize the following: (1) the prevalence of sarcopenia in patients with fragility fracture and (2) the associated risk factors for fragility fracture in patients with sarcopenia. Literature search was conducted in PubMed and Cochrane databases. Studies with the prevalence of sarcopenia in elderly patients with fragility fracture and associated risk factors in patients with sarcopenia were included. A total of 15 papers were included, with 10 reporting sarcopenia prevalence, and 5 on fracture risk in patients with sarcopenia. The prevalence of sarcopenia after fracture ranged from 12.4 to 95% in males and 18.3 to 64% in females. The prevalence of sarcopenia in elderly patients with fragility fracture was high, especially in men. Two studies showed that sarcopenia was a risk factor for fragility fracture when associated with low bone mineral density (BMD) but only in men. Caution should be taken for male patients with sarcopenia and low BMD, which is related to significantly increased risk of fractures. There is a pressing need for further research on sarcopenia and its risk on fragility fracture to better understand the relationship, pathophysiology, and mechanisms, which may shed light on potential interventions to improve clinical outcomes.
View details for DOI 10.1007/s00198-018-04828-0
View details for Web of Science ID 000461576600002
View details for PubMedID 30610245
Impaired fracture healing in sarco-osteoporotic mice can be rescued by vibration treatment through myostatin suppression.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
Sarcopenia is highly prevalent in fragility fracture patients and is associated with delayed healing. In this study, we investigated the effect of Low-Magnitude High-Frequency Vibration (LMHFV) on osteoporotic fracture with sarcopenia and the potential role of myostatin. Osteoporotic fractures created in sarcopenic SAMP8, non-sarcopenic SAMR1 were randomized to control or LMHFV (SAMP8, SAMR1, SAMP8-V or SAMR1-V) groups. Healing and myostatin expression were evaluated at 2, 4, and 6 weeks post-fracture. In vitro, conditioned-media were collected from myofibers isolated from aged and young SAMP8 or C2C12 myoblasts with or without LMHFV. Osteoblastic MC3T3-E1 under osteogenic differentiation were treated with plain or conditioned-medium (+/- myostatin propeptide). LMHFV significantly enhanced callus formation was in non-sarcopenic SAMR1 mice; but the enhancement effect was not significant in SAMP8 mice at week 2. Myostatin expressions in callus and biceps femoris of SAMP8 group were significantly higher all groups with significant negative correlation with callus size (R2 =0.7256; p=0.0004). Mechanical properties (week 4) and callus remodeling (week 6) were inferior in SAMP8 versus SAMR1 and were significantly enhanced by LMHFV. ALP and Runx2 expression of MC3T3-E1 was lower in aged myofiber compared to young, but up-regulated by LMHFV or myostatin inhibition; also confirmed with C2C12. LMHFV enhanced early callus formation, microarchitecture, callus remodeling and mechanical properties of fracture healing in both SAMP8 and SAMR1; however, more effective in non-sarcopenic SAMR1 mice. Impaired fracture healing in sarcopenic SAMP8 mice is attributed by elevated myostatin expression in callus and muscle, which correlated negatively with callus formation. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/jor.24477
View details for PubMedID 31535727
Vibration treatment modulates macrophage polarisation and enhances early inflammatory response in oestrogen-deficient osteoporotic-fracture healing.
European cells & materials
2019; 38: 228–45
Fracture healing is a well-orchestrated and coordinated process and begins with the inflammatory stage involving the infiltration of immune cells and the release of cytokines, including tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). Low-magnitude high-frequency vibration (LMHFV) stimulation is effective in promoting fracture healing. The study hypothesis was that the innate immune response was impaired in osteoporotic fracture and LMHFV could positively modulate it. 9-month-old ovariectomy (OVX)-induced osteoporotic rats were randomised into sham (SHAM), OVX control (OVX), OVX-vibration (OVX-VT) or OVX vibration plus administration of COX-2 specific non-steroid anti-inflammatory drugs (OVX-VT-NSAID). LMHFV (35 Hz, 0.3 g) was given 20 min/d and 5 d/week to the treatment groups. Healing and innate immune response were evaluated by weekly radiographs, endpoint micro-computed tomography (µCT), enzyme-linked immunosorbent assay (ELISA) and histomorphometry at weeks 1, 2, 4 and 8 post-treatment. Results showed that OVX slightly elevated systemic inflammation but impaired the innate immune response locally at the fracture site, with significantly lower expressions of TNF-α and IL-6 but higher IL-10 expression during the early stage of healing. LMHFV was effective in accelerating the delayed fracture healing in OVX bones by partly restoring the impaired innate immune response at the fracture site, accompanied by promoted progression of macrophage polarisation from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype. In conclusion, vibration treatment could positively modulate the impaired innate immune response and promote macrophage polarisation in osteoporotic-fracture healing.
View details for DOI 10.22203/eCM.v038a16
View details for PubMedID 31697398
Functionalized cellulose beads with three dimensional porous structure for rapid adsorption of active constituents from Pyrola incarnata
2018; 181: 560–69
In the present study, porous magnetic cellulose beads (CBs) were prepared and further modified using amines. The CBs appeared to have good spherical shape and three-dimensional (3D) porous structure. In the adsorption tests, the modified cellulose beads (MCBs) showed better adsorption capacities and shorter adsorption times on hyperin and 2'-O-galloylhyperin than the commercial resins. The adsorption may be due to the hydrogen bonding between the target compounds and the amine groups of MCBs. After adsorption and desorption, the contents of hyperin and 2'-O-galloylhyperin reached 1.32% and 3.92%, which were 4.08 and 4.23 times higher than those in the Pyrola extracts. Therefore, the prepared MCBs in this study make an excellent adsorbing material of hyperin and 2'-O-galloylhyperin, and it may have potential for the separation of other natural compounds.
View details for DOI 10.1016/j.carbpol.2017.11.111
View details for Web of Science ID 000418661000065
View details for PubMedID 29254008
TNF-alpha inhibits SATB2 expression and osteoblast differentiation through NF-kappa B and MAPK pathways
2018; 9 (4): 4833–50
Although the mechanisms of Tumor necrosis factor alpha (TNF-α) on facilitating osteoclast differentiation and bone resorption is well known, the mechanisms behind the suppression of the osteoblast differentiation from mesenchymal stem cells (MSCs) are still poorly understood. In this study, we observed a negative correlation between TNF-α levels and the expression of special AT-rich sequence-binding protein 2 (SATB2), a critical osteoblastogenesis transcription factor, in ovariectomy (OVX)-induced bone loss and IL-1-induced arthritis animal model. We found that TNF-α treatment inhibited mesenchymal cell line C2C12 osteoblast differentiation and sharply decreased BMP2-induced SATB2 expression. Upon TNF-α treatment, the activity of smad1/5/8 was inhibited, by contrast, extracellular signal-regulated kinase-1/2 (ERK1/2) and P38 was increased in C2C12 cells, the inhibitor of ERK1/2 (U0126) was found to abrogate the TNF-α inhibition of SATB2 expression. Furthermore, the NF-κB signaling pathway in C2C12 cells was significantly activated by the treatment of TNF-α, and TNF-α induced NF-κB directly binds to SATB2 promoter to suppress its expression. These results suggest that TNF-α suppresses SATB2 expression through activating NF-κB and MAPK signaling and depressing smad1/5/8 signaling, which contributes to the inhibition of osteoblast differentiation and might be potential therapeutic targets for inflammation-induced bone loss.
View details for DOI 10.18632/oncotarget.23373
View details for Web of Science ID 000422651700045
View details for PubMedID 29435145
View details for PubMedCentralID PMC5797016
An animal model of co-existing sarcopenia and osteoporotic fracture in senescence accelerated mouse prone 8 (SAMP8)
2017; 97: 1–8
Sarcopenia and osteoporotic fracture are common aging-related musculoskeletal problems. Recent evidences report that osteoporotic fracture patients showed high prevalence of sarcopenia; however, current clinical practice basically does not consider sarcopenia in the treatment or rehabilitation of osteoporotic fracture. There is almost no report studying the relationship of the co-existing of sarcopenia and osteoporotic fracture healing. In this study, we validated aged senescence accelerated mouse prone 8 (SAMP8) and senescence accelerated mouse resistant 1 (SAMR1) as animal models of senile osteoporosis with/without sarcopenia. Bone mineral density (BMD) at the 5th lumbar and muscle testing of the two animal strains were measured to confirm the status of osteoporosis and sarcopenia, respectively. Closed fracture was created on the right femur of 8-month-old animals. Radiographs were taken weekly post-fracture. MicroCT and histology of the fractured femur were performed at week 2, 4 and 6 post-fracture, while mechanical test of both femora at week 4 and 6 post-fracture. Results showed that the callus of SAMR1 was significantly larger at week 2 but smaller at week 6 post-fracture than SAMP8. Mechanical properties were significantly better at week 4 post-fracture in SAMR1 than SAMP8, indicating osteoporotic fracture healing was delayed in sarcopenic SAMP8. This study validated an animal model of co-existing sarcopenia and osteoporotic fracture, where a delayed fracture healing might be resulted in the presence of sarcopenia.
View details for DOI 10.1016/j.exger.2017.07.008
View details for Web of Science ID 000410651200001
View details for PubMedID 28711604
Ultrasound as a stimulus for musculoskeletal disorders
JOURNAL OF ORTHOPAEDIC TRANSLATION
2017; 9: 52–59
Ultrasound is an inaudible form of acoustic sound wave at 20 kHz or above that is widely used in the medical field with applications including medical imaging and therapeutic stimulation. In therapeutic ultrasound, low-intensity pulsed ultrasound (LIPUS) is the most widely used and studied form that generally uses acoustic waves at an intensity of 30 mW/cm2, with 200 ms pulses and 1.5 MHz. In orthopaedic applications, it is used as a biophysical stimulus for musculoskeletal tissue repair to enhance tissue regeneration. LIPUS has been shown to enhance fracture healing by shortening the time to heal and reestablishment of mechanical properties through enhancing different phases of the healing process, including the inflammatory phase, callus formation, and callus remodelling phase. Reports from in vitro studies reveal insights in the mechanism through which acoustic stimulations activate cell surface integrins that, in turn, activate various mechanical transduction pathways including FAK (focal adhesion kinase), ERK (extracellular signal-regulated kinase), PI3K, and Akt. It is then followed by the production of cyclooxygenase 2 and prostaglandin E2 to stimulate further downstream angiogenic, osteogenic, and chondrogenic cytokines, explaining the different enhancements observed in animal and clinical studies. Furthermore, LIPUS has also been shown to have remarkable effects on mesenchymal stem cells (MSCs) in musculoskeletal injuries and tissue regeneration. The recruitment of MSCs to injury sites by LIPUS requires the SDF-1 (stromal cell derived factor-1)/CXCR-4 signalling axis. MSCs would then differentiate differently, and this is regulated by the presence of different cytokines, which determines their fates. Other musculoskeletal applications including bone-tendon junction healing, and distraction osteogenesis are also explored, and the results are promising. However, the use of LIPUS is controversial in treating osteoporosis, with negative findings in clinical settings, which may be attributable to the absence of an injury entry point for the acoustic signal to propagate, strong attenuation effect of cortical bone and the insufficient intensity for penetration, whereas in some animal studies it has proven effective.
View details for DOI 10.1016/j.jot.2017.03.004
View details for Web of Science ID 000405123100007
View details for PubMedID 29662799
View details for PubMedCentralID PMC5822964
In Vivo Identification and Induction of Articular Cartilage Stem Cells by Inhibiting NF-kappa B Signaling in Osteoarthritis
2015; 33 (10): 3125–37
Osteoarthritis (OA) is a highly prevalent and debilitating joint disorder characterized by the degeneration of articular cartilage. However, no effective medical therapy has been found yet for such condition. In this study, we directly confirmed the existence of articular cartilage stem cells (ACSCs) in vivo and in situ for the first time both in normal and OA articular cartilage, and explored their chondrogenesis in Interleukin-1β (IL-1β) induced inflammation environment and disclose whether the inhibition of NF-κB signaling can induce ACSCs activation thus improve the progression of experimental OA. We found an interesting phenomenon that ACSCs were activated and exhibited a transient proliferative response in early OA as an initial attempt for self-repair. During the in vitro mechanism study, we discovered IL-1β can efficiently activate the NF-κB pathway and potently impair the responsiveness of ACSCs, whereas the NF-κB pathway inhibitor rescued the ACSCs chondrogenesis. The final in vivo experiments further confirmed ACSCs' activation were maintained by NF-κB pathway inhibitor, which induced cartilage regeneration, and protected articular cartilage from injury in an OA animal model. Our results provided in vivo evidence of the presence of ACSCs, and disclosed their action in the early OA stage and gradual quiet as OA process, presented a potential mechanism for both cartilage intrinsic repair and its final degradation, and demonstrated the feasibility of inducing endogenous adult tissue-specific mesenchymal stem cells for articular cartilage repair and OA therapy.
View details for DOI 10.1002/stem.2124
View details for Web of Science ID 000363264500022
View details for PubMedID 26285913
An updated review of mechanotransduction in skin disorders: transcriptional regulators, ion channels, and microRNAs
CELLULAR AND MOLECULAR LIFE SCIENCES
2015; 72 (11): 2091–2106
The skin is constantly exposed and responds to a wide range of biomechanical cues. The mechanobiology of skin has already been known and applied by clinicians long before the fundamental molecular mechanisms of mechanotransduction are elucidated.Despite increasing knowledge on the mediators of biomechanical signaling such as mitogen-associated protein kinases, Rho GTPases or FAK-ERK pathways, the key elements of mechano-responses transcription factors, and mechano-sensors remain unclear. Recently, canonical biochemical components of Hippo and Wnt signaling pathway YAP and β-catenin were found to exhibit undefined mechanical sensitivity. Mechanical forces were identified to be the dominant regulators of YAP/TAZ activity in a multicellular context. Furthermore, different voltage or ligand sensitive ion channels in the cell membrane exhibited their mechanical sensitivity as mechano-sensors. Additionally, a large number of microRNAs have been confirmed to regulate cellular behavior and contribute to various skin disorders under mechanical stimuli. Mechanosensitive (MS) microRNAs could not only be activated by distinct mechanical force pattern, but also responsively target MS sensors such as e-cadherin and cytoskeleton constituent RhoA.Thus, a comprehensive understanding of this regulatory network of cutaneous mechanotransduction will facilitate the development of novel approaches to wound healing, hypertrophic scar formation, skin regeneration, and the progression or initiation of skin diseases.
View details for DOI 10.1007/s00018-015-1853-y
View details for Web of Science ID 000354883800004
View details for PubMedID 25681865
Identification of biomechanical force as a novel inducer of epithelial-mesenchymal transition features in mechanical stretched skin
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
2015; 7 (11): 2187–98
Biomechanical cues of the microenvironment are recognized as potent regulators of cell behaviors. Skin regeneration induced by tissue expansion has been confirmed by results of experimental and clinical studies. However, it is still unknown whether skin regeneration induced by mechanical factor is the same biological process as skin morphogenesis during embryonic development. In order to explore the potential role of biomechanical force (BioF) in skin regeneration and whether epithelial-mesenchymal transition (EMT) is induced by BioF, continuous mechanical tension (CMT) at 10% elongation was applied to human keratinocytes in vitro for 12, 24, 48 and 72 hours. Cell proliferation and differentiation were analyzed, including the expression of markers of EMT: vimentin, FSP1, E-cadherin and N-cadherin. Normal and mechanical stretched skin specimens collected from mice were examined by immunofluorescence analysis and RT-PCR. We found that BioF promoted the proliferation and inhibited differentiation of keratinocytes in vitro. The expression of markers of EMT vimentin, FSP1, E-cadherin and N-cadherin were transiently up-regulated by BioF. Keratinocytes activation, epidermal thickening and EMT features were also observed in the stretched epidermis of mice, compared to normal mice. Furthermore, the mechanism of BioF induced EMT was found to be the enhanced autocrine effect of TNF-α, in part, and direct activation of the NF-κB pathway. Collectively, BioF promoted the proliferation of keratinocytes by transiently inducing some EMT features. BioF, as a vital biomechanical cue of the microenvironment of skin, was identified to be a novel inducer of EMT, regulating keratinocytes' proliferation, differentiation and homeostasis of skin tissue.
View details for Web of Science ID 000367671500005
View details for PubMedID 26807167
View details for PubMedCentralID PMC4697699
A heterocyclic molecule kartogenin induces collagen synthesis of human dermal fibroblasts by activating the smad4/smad5 pathway
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
2014; 450 (1): 568–74
Declined production of collagen by fibroblasts is one of the major causes of aging appearance. However, only few of compounds found in cosmetic products are able to directly increase collagen synthesis. A novel small heterocyclic compound called kartogenin (KGN) was found to stimulate collagen synthesis of mesenchymal stem cells (MSCs). So, we hypothesized and tested that if KGN could be applied to stimulate the collagen synthesis of fibroblasts. Human dermal fibroblasts in vitro were treated with various concentrations of KGN, with dimethyl sulfoxide (DMSO) serving as the negative control. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunofluorescence analyses were performed to examine the expression of collagen and transforming growth factor beta (TGF-β) signaling pathway. The production of collagen was also tested in vivo by Masson's trichrome stain and immunohistochemistry in the dermis of mice administrated with KGN. Results showed that without obvious influence on fibroblasts' apoptosis and viability, KGN stimulated type-I collagen synthesis of fibroblasts at the mRNA and protein levels in a time-dependent manner, but KGN did not induce expression of α-skeletal muscle actin (α-sma) or matrix metallopeptidase1 (MMP1), MMP9 in vitro. Smad4/smad5 of the TGF-β signaling pathway was activated by KGN while MAPK signaling pathway remained unchanged. KGN also increased type-I collagen synthesis in the dermis of BALB/C mice. Our results indicated that KGN promoted the type-I collagen synthesis of dermal fibroblasts in vitro and in the dermis of mice through activation of the smad4/smad5 pathway. This molecule could be used in wound healing, tissue engineering of fibroblasts, or aesthetic and reconstructive procedures.
View details for DOI 10.1016/j.bbrc.2014.06.016
View details for Web of Science ID 000343641000093
View details for PubMedID 24928394
Dexamethasone shifts bone marrow stromal cells from osteoblasts to adipocytes by C/EBPalpha promoter methylation
CELL DEATH & DISEASE
2013; 4: e832
Dexamethasone (Dex)-induced osteoporosis has been described as the most severe side effect in long-term glucocorticoid therapy. The decreased bone mass and the increased marrow fat suggest that Dex possibly shifts the differentiation of bone marrow stromal cells (BMSCs) to favor adipocyte over osteoblast, but the underlying mechanisms are still unknown. In this paper, we established a Dex-induced osteoporotic mouse model, and found that BMSCs from Dex-treated mice are more likely to differentiate into adipocyte than those from control mice, even under the induction of bone morphogenetic protein-2 (BMP2). We also discovered both in vitro and in vivo that the expression level of adipocyte regulator CCAAT/enhancer-binding protein alpha (C/EBPalpha) is significantly upregulated in Dex-induced osteoporotic BMSCs during osteoblastogenesis by a mechanism that involves inhibited DNA hypermethylation of its promoter. Knockdown of C/EBPalpha in Dex-induced osteoporotic cells rescues their differentiation potential, suggesting that Dex shifts BMSC differentiation by inhibiting C/EBPalpha promoter methylation and upregulating its expression level. We further found that the Wnt/beta-catenin pathway is involved in Dex-induced osteoporosis and C/EBPalpha promoter methylation, and its activation by LiCl rescues the effect of Dex on C/EBPalpha promoter methylation and osteoblast/adipocyte balance. This study revealed the C/EBPalpha promoter methylation mechanism and evaluated the function of Wnt/beta-catenin pathway in Dex-induced osteoporosis, providing a useful therapeutic target for this type of osteoporosis.
View details for DOI 10.1038/cddis.2013.348
View details for Web of Science ID 000326967100018
View details for PubMedID 24091675
View details for PubMedCentralID PMC3824658