Callus formation is related to the expression ratios of estrogen receptors-alpha and -beta in ovariectomy-induced osteoporotic fracture healing

Chow, Simon Kwoon‐Ho; Leung, Kwok‐Sui; Qin, Ling; Wei, Fulan; Cheung, Wing-Hoi

doi:10.1007/s00402-014-2070-0

Cited by 30 publications

(32 citation statements)

References 45 publications

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“…The relationships between key repair genes may provide additional insights into the repair process, and in fact gene expression ratios have been utilized to examine tissue healing trends in musculoskeletal tissues, including bone 47 and ligament. 48 In this study, normal TA muscle tissue ratios (ECM:MyoD) ranged between 10 and 15 for each of the ECM genes measured.…”

Section: Decellularized Skeletal Muscle With Minced Muscle Autograftsmentioning

confidence: 99%

Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

Kasukonis

Kim

Brown

et al. 2016

Tissue Engineering Part A

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Skeletal muscle is capable of robust self-repair following mild trauma, yet in cases of traumatic volumetric muscle loss (VML), where more than 20% of a muscle's mass is lost, this capacity is overwhelmed. Current autogenic whole muscle transfer techniques are imperfect, which has motivated the exploration of implantable scaffolding strategies. In this study, the use of an allogeneic decellularized skeletal muscle (DSM) scaffold with and without the addition of minced muscle (MM) autograft tissue was explored as a repair strategy using a lower-limb VML injury model (n = 8/sample group). We found that the repair of VML injuries using DSM + MM scaffolds significantly increased recovery of peak contractile force (81 -3% of normal contralateral muscle) compared to unrepaired VML controls (62 -4%). Similar significant improvements were measured for restoration of muscle mass (88 -3%) in response to DSM + MM repair compared to unrepaired VML controls (79 -3%). Histological findings revealed a marked decrease in collagen dense repair tissue formation both at and away from the implant site for DSM + MM repaired muscles. The addition of MM to DSM significantly increased MyoD expression, compared to isolated DSM treatment (21-fold increase) and unrepaired VML (37-fold) controls. These findings support the further exploration of both DSM and MM as promising strategies for the repair of VML injury.

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Section: Decellularized Skeletal Muscle With Minced Muscle Autograftsmentioning

confidence: 99%

Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

Kasukonis

Kim

Brown

et al. 2016

Tissue Engineering Part A

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“…Comparing the above results, the OVX‐VT group exhibited a more positive response to LMHFV than the SHAM‐VT group in terms of the osteocytes’ morphology, expression of markers, bone parameters, mechanical properties, and mineralization status. The greater enhancement effect of LMHFV on the osteoporotic bone is likely to be related to the increment of estrogen receptor (ER), which acts as mechanical signal transduction molecules and exhibits delayed expression in ovariectomy‐induced osteoporotic fracture . Of the various bone cells that are known to express ER‐α, a subsiding ER‐α expression was observed specifically in osteocytes after the menopause in older women .…”

Section: Discussionmentioning

confidence: 99%

“…The greater enhancement effect of LMHFV on the osteoporotic bone is likely to be related to the increment of estrogen receptor (ER), which acts as mechanical signal transduction molecules and exhibits delayed expression in ovariectomy-induced osteoporotic fracture. 59,60 Of the various bone cells that are known to express ER-α, a subsiding ER-α expression was observed specifically in osteocytes after the menopause in older women. 61 With reference to our previous report, LMHFV can enhance ER-α expression in OVX-induced osteoporotic fracture healing, with improved mechanical signal transduction and callus formation.…”

Section: F I G U R Ementioning

confidence: 99%

Can we enhance osteoporotic metaphyseal fracture healing through enhancing ultrastructural and functional changes of osteocytes in cortical bone with low‐magnitude high‐frequency vibration?

Choy

Wong

et al. 2020

FASEB j.

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Fragility fractures are related to the loss of bone integrity and deteriorated morphology of osteocytes. Our previous studies have reported that low‐magnitude high‐frequency vibration (LMHFV) promoted osteoporotic fracture healing. As osteocytes are known for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance osteoporotic fracture healing through enhancing morphological changes in the osteocyte lacuna‐canalicular network (LCN) and mineralization. A metaphyseal fracture model was established in female Sprague‐Dawley rats to investigate changes in osteocytes and healing outcomes from early to late phase post‐fracture. Our results showed that the LCN exhibited an exuberant outgrowth of canaliculi in the osteoporotic fractured bone at day 14 after LMHFV. LMHFV upregulated the E11, dentin matrix protein 1 (DMP1), and fibroblast growth factor 23 (FGF23), but downregulated sclerostin (Sost) in osteocytes. Moreover, LMHFV promoted mineralization with significant enhancements of Ca/P ratio, mineral apposition rate (MAR), mineralizing surface (MS/BS), and bone mineral density (BMD) in the osteoporotic group. Consistently, better healing was confirmed by microarchitecture and mechanical properties, whereas the enhancement in osteoporotic group was comparable or even greater than the normal group. This is the first report to reveal the enhancement effect of LMHFV on the osteocytes’ morphology and functions in osteoporotic fracture healing.

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“…For myostatin, TNF‐α and BMP‐2 detection, a secondary goat‐anti‐rabbit AlexaFluor‐488 antibody was used (Invitrogen, Thermo Fisher Scientific, Carlsbad, CA). Images were captured on a fluorescence microscope and the positive area fraction was quantified using ImageJ (NIH, Bethesda, MD) as previously described …”

Section: Methodsmentioning

confidence: 99%

“…No non‐specific amplification was confirmed by the dissociation curve analysis. Data were analyzed by the ΔΔ C t method against the housekeeping gene of glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) …”

Section: Methodsmentioning

confidence: 99%

Impaired Fracture Healing in Sarco‐Osteoporotic Mice Can Be Rescued by Vibration Treatment Through Myostatin Suppression

Zhang

Chim

Wang

et al. 2019

Journal Orthopaedic Research

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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 (R 2 = 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. Alkaline Phosphatase (ALP) and Runx2 expression of MC3T3-E1 was lower in aged myofiber compared with young, but upregulated 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.

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Callus formation is related to the expression ratios of estrogen receptors-alpha and -beta in ovariectomy-induced osteoporotic fracture healing

Abstract: We conclude that the delayed healing rate and impaired callus quality in OVX-induced osteoporotic fracture is related to the delayed expression of ERs. A high ER-α:ER-β ratio favors callus formation.

Cited by 30 publications

References 45 publications

Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

Can we enhance osteoporotic metaphyseal fracture healing through enhancing ultrastructural and functional changes of osteocytes in cortical bone with low‐magnitude high‐frequency vibration?

Impaired Fracture Healing in Sarco‐Osteoporotic Mice Can Be Rescued by Vibration Treatment Through Myostatin Suppression

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