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Ficus deltoidea Prevented Bone Loss in Preclinical Osteoporosis/Osteoarthritis Model by Suppressing Inflammation

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Abstract

Osteoporosis (OP) and osteoarthritis (OA) are debilitating musculoskeletal diseases of the elderly. Ficus deltoidea (FD) or mistletoe fig, a medicinal plant, was pre-clinically evaluated against OP- and OA-related bone alterations, in postmenopausal OA rat model. Thirty twelfth-week-old female rats were divided into groups (n = 6). Four groups were bilateral ovariectomized (OVX) and OA-induced by intra-articular monosodium iodoacetate (MIA) injection into the right knee joints. The Sham control and OVX-OA non-treated groups were given deionized water. The three other OVX-OA groups were orally administered daily with FD extract (200, 400 mg/kg) or diclofenac (5 mg/kg) for 4 weeks. The rats’ bones and blood were evaluated for protein and mRNA expressions of osteoporosis and inflammatory indicators, and micro-CT computed tomography for bone microstructure. The non-treated OVX-OA rats developed severe OP bone loss and bone microstructural damage in the subchondral and metaphyseal regions, supported by reduced serum bone formation markers (osteocalcin, osteoprotegerin) and increased bone resorption markers (RANKL and CTX-I). The FD extract significantly (p < 0.05) mitigated these bone microstructural and biomarker changes by dose-dependently down-regulating pro-inflammatory NF-κβ, TNF-α, and IL-6 mRNA expressions. The FD extract demonstrated good anti-osteoporotic properties in this OP/OA preclinical model by stimulating bone formation and suppressing bone resorption via anti-inflammatory pathways. This is among the few reports relating the subchondral bone plate and trabecular thickening with the metaphyseal trabecular osteopenic bone loss under osteoporotic-osteoarthritis conditions, providing some insights on the debated inverse relationship between osteoporosis and osteoarthritis.

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Acknowledgements

We acknowledge the Ministry of Agriculture, Herbal development Division for the research grant; Universiti Putra Malaysia for the facilities; and Comparative Medicine and Technology (CoMeT) Unit and Institute of Bioscience, Universiti Putra Malaysia for the assistance in performing all-animal-related procedures.

Funding

This work was supported by the Herbal Development Division, Ministry of Agriculture, Malaysia (Grant No. NH1014D052).

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Authors and Affiliations

  1. UPM-MAKNA Laboratory of Cancer Research, Institute of Bioscience, Universiti Putra Malaysia, UPM, 43400, Serdang, Selangor, Malaysia

    Nur Adeelah Che Ahmad Tantowi & Suhaila Mohamed

  2. Faculty of Veterinary Medicine, Universiti Putra Malaysia, UPM, Serdang, Malaysia

    Seng Fong Lau

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  1. Nur Adeelah Che Ahmad Tantowi
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Correspondence to Suhaila Mohamed.

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Nur Adeelah Che Ahmad Tantowi, Seng Fong Lau, and Suhaila Mohamed declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted [Institutional Animal Care and Use Committee (IACUC), Universiti Putra Malaysia (UPM/IACUC/AUPR083/2014)].

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Che Ahmad Tantowi, N.A., Lau, S.F. & Mohamed, S. Ficus deltoidea Prevented Bone Loss in Preclinical Osteoporosis/Osteoarthritis Model by Suppressing Inflammation. Calcif Tissue Int 103, 388–399 (2018). https://doi.org/10.1007/s00223-018-0433-1

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