Abstract
To investigate the osteoinductive mechanism triggered by hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) biomaterials in mice which keep exercising. Methods: The HA/β-TCP biomaterials were implanted in the muscle of bilateral thighs (non-osseous sites) of eighty Balb/C mice. All animals were then randomly divided into 4 groups (n = 20). In group 1 (negative control group), the mice were fed routinely. In group 2 (running group), all mice were put on a treadmill which was set to a 60-degree incline. The mice ran 20 min thrice each day. A 5-minute break was included in the routine from day three onwards. In group 3 (weight-bearing group), all mice underwent weight-bearing running. The mice in this group performed the same routine as group 2 while carrying 5 g rubber weights. In group 4 (positive control group), dexamethasone was injected in the implanted sites of the biomaterials from the day of the operation. All mice were injected once per week and received a total of 8 injections. One and eight weeks after surgery, the blood serum was collected to detect inflammatory and immunological factors by ELISA. In addition to this, biomaterial specimens were obtained to observe inflammatory and osteogenic levels via histological staining and to facilitate analysis of the osteogenic mechanism by Western Blot. Results: The inflammation indexes caused by surgery were alleviated through running or weight-bearing running: The tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were significantly reduced in groups 2 and 3 at week 8. Exercise also enhanced the secretion of interferon-γ (IFN-γ) in mice; this can strengthen their immunity. The new bone tissues were observed in all groups; however, the area percentage of new bone tissues and the number of osteoblasts were highest in the weight-bearing group. Furthermore, the key proteins of wingless/integrated (Wnt) signaling pathway, Wnt1, Wnt3a, and β-catenin, were up-regulated during osteoinduction. This up-regulation activated runt-related transcription factor-2 (Runx2), increased the expression of osteopontin (OPN) and osteocalcin (OCN). Conclusion: Weight-bearing exercise can promote the bone and bone marrow formation through the Wnt signaling pathway: Observations documented here suggest that the proper exercise is beneficial to the recovery of bone damage.
Highlights
Common bone injuries or defects are often occasionally a difficult period of recovery for patients.For single osteoporosis-related fractures, the number of patients is forecasted to exceed 3 million per year by 2025 in the USA [1]
Inflammatory reactions were observed in hematoxylin and eosin (HE) sections, in addition to this, typical inflammatory factors, tumor necrosis factor-α (TNF-α) and IL-6 levels in serum were detected by enzyme-linked immunosorbent assay (ELISA)
The results showed that the expression of all the three proteins had been significantly up-regulated in groups 3 and 4 in contrast to group 1, while the neonatal bone was used as control (Figure 6A), indicating that both exercise and dexamethasone could enhance bone induction to stimulate the generation of new bone tissues through activation of RUNX2 pathway
Summary
Common bone injuries or defects are often occasionally a difficult period of recovery for patients.For single osteoporosis-related fractures, the number of patients is forecasted to exceed 3 million per year by 2025 in the USA [1]. Common bone injuries or defects are often occasionally a difficult period of recovery for patients. Synthetic biomaterials have been identified as promising scaffolds to Metabolites 2020, 10, 90; doi:10.3390/metabo10030090 www.mdpi.com/journal/metabolites. Scaffolds are biomaterials that are designed to properly match the natural structure and properties of bone, and they enhance all the biological processes involved in bone formation. Scaffolds are implanted in areas that require bone tissue or bone grafts due to several reasons including severe bone loss after trauma, large bone defects, tumor removal, or some reconstructive surgeries. An additional development in this field that supports the use of synthetic biomaterials is the emergence of an algorithm, based on mechanical biology, capable of predicting the optimal load for scaffolds: scaffolds under optimal load facilitate larger amounts of bone formation [3]. Recent advances in the application of mesenchymal stem cells in tissue engineering, in terms of their ability to promote wound healing and tissue regeneration, provide new ways to improve complex treatments that require bone regeneration [4]
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