Modulation of bone turnover aberration: A target for management of primary osteoporosis in experimental rat model
Enas A Fouad-Elhady1, Hadeer A Aglan2,3, Rasha E Hassan1
1Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Abstract:
Osteoporosis is a skeletal degenerative disease characterised by abnormal bone turnover with scant bone formation and overabundant bone resorption. The present approach was intended to address the potency of nanohydroxyapatite (nHA), chitosan/hydroxyapatite nanocomposites (nCh/HA) and silver/hydroxyapatite nanoparticles (nAg/HA) to modulate bone turnover deviation in primary osteoporosis induced in the experimental model. Characterisation techniques such as TEM, zeta-potential, FT-IR and XRD were used to assess the morphology, the physical as well as the chemical features of the prepared nanostructures. The in vivo experiment was conducted on forty-eight adult female rats, randomised into 6 groups (8 rats/group), (1) gonad-intact, (2) osteoporotic group, (3) osteoporotic + nHA, (4) osteoporotic + nCh/HA, (5) osteoporotic + nAg/HA and (6) osteoporotic + alendronate (ALN). After three months of treatment, serum sclerostin (SOST), bone alkaline phosphatase (BALP) and bone sialoprotein (BSP) levels were quantified using ELISA. Femur bone receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) and cathepsin K (CtsK) mRNA levels were evaluated by quantitative RT-PCR. Moreover, alizarin red S staining was applied to determine the mineralisation intensity of femur bone. Findings in the present study indicated that treatment with nHA, nCh/HA or nAg/HA leads to significant repression of serum SOST, BALP and BSP levels parallel to a significant down-regulation of RANKL and CtsK gene expression levels. On the other side, significant enhancement in the calcification intensity of femur bone has been noticed. The outcomes of this experimental setting ascertained the potentiality of nHA, nCh/HA and nAg/HA as promising nanomaterials in attenuating the excessive bone turnover in the primary osteoporotic rat model. The mechanisms behind the efficacy of the investigated nanostructures involved the obstacle of serum and tissue indices of bone resorption besides the strengthening of bone mineralisation.
Insights
Nanoparticles including nanohydroxyapatite (nHA), chitosan/hydroxyapatite (nCh/HA), and silver/hydroxyapatite (nAg/HA) show promise in treating osteoporosis. These nanomaterials effectively reduced bone resorption and enhanced bone mineralization in an experimental rat model.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Orthopedics
- Pharmacology
Background:
- Osteoporosis is a degenerative bone disease characterized by imbalanced bone turnover, with reduced formation and increased resorption.
- Current treatments aim to modulate this abnormal bone remodeling process.
Purpose of the Study:
- To evaluate the efficacy of nanohydroxyapatite (nHA), chitosan/hydroxyapatite nanocomposites (nCh/HA), and silver/hydroxyapatite nanoparticles (nAg/HA) in modulating bone turnover in a primary osteoporosis rat model.
- To investigate the underlying mechanisms of these nanomaterials in attenuating excessive bone resorption and enhancing bone mineralization.
Main Methods:
- Characterization of nanostructures using TEM, zeta-potential, FT-IR, and XRD.
- An in vivo study involving 48 female rats with induced primary osteoporosis, randomized into 6 groups (including controls and alendronate treatment).
- Assessment of serum markers (SOST, BALP, BSP), gene expression (RANKL, CtsK), and bone mineralization (alizarin red S staining) after three months of treatment.
Main Results:
- Treatment with nHA, nCh/HA, and nAg/HA significantly reduced serum levels of sclerostin (SOST), bone alkaline phosphatase (BALP), and bone sialoprotein (BSP).
- These nanomaterials also led to significant downregulation of RANKL and CtsK gene expression, indicating reduced bone resorption.
- A significant enhancement in femur bone calcification intensity was observed in the treatment groups.
Conclusions:
- Nanohydroxyapatite (nHA), chitosan/hydroxyapatite nanocomposites (nCh/HA), and silver/hydroxyapatite nanoparticles (nAg/HA) demonstrate significant potential in mitigating excessive bone turnover in osteoporosis.
- The therapeutic effects are attributed to the inhibition of bone resorption markers and the promotion of bone mineralization.
- These nanomaterials represent promising therapeutic agents for managing osteoporosis.
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