Preprint / Version 1

Cissus quadrangularis (Hadjod) Inhibits RANKL-Induced Osteoclastogenesis and Augments Bone Health in an Estrogen-Deficient Preclinical Model of Osteoporosis Via Modulating the Host Osteoimmune System

Authors

  • Zaffar Azam Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
  • Leena Sapra Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
  • Kalpana Baghel Department of Zoology, Dr. Harisingh Gour Vishwavidyalaya (Central University), Sagar 470003, India
  • Niharika Sinha Drug Development Laboratory, School of Vocational Studies and Applied Sciences, Gautam Buddha University, Greater Noida 201312, India
  • Rajesh Gupta Drug Development Laboratory, School of Vocational Studies and Applied Sciences, Gautam Buddha University, Greater Noida 201312, India
  • Vandana Soni Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar 470003, India
  • Chaman Saini Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
  • Pradyumna Mishra Department of Molecular Biology, ICMR-NIREH, Bhopal 462001, India
  • Rupesh Srivastava Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India

Keywords:

Cissus quadrangularis, osteoporosis, immunoporosis, Th17, Tregs, Bregs

Abstract

Osteoporosis is a systemic skeletal disease characterised by low bone mineral density (BMD), degeneration of bone micro-architecture, and impaired bone strength. Cissus quadrangularis (CQ), popularly known as Hadjod (bone setter) in Hindi, is a traditional medicinal herb exhibiting osteoprotective potential in various bone diseases, especially osteoporosis and fractures. However, the cellular mechanisms underpinning its direct effect on bone health through altering the host immune system have never been elucidated. In the present study, we interrogated the osteoprotective and immunoporotic (the osteoprotective potential of CQ via modulating the host immune system) potential of CQ in preventing inflammatory bone loss under oestrogen-deficient conditions. The current study outlines the CQ’s osteoprotective potential under both ex vivo and in vivo (ovariectomized) conditions. Our ex vivo data demonstrated that, in a dose-dependent manner CQ, suppresses the RANKL-induced osteoclastogenesis (p < 0.001) as well as inhibiting the osteoclast functional activity (p < 0.001) in mouse bone marrow cells (BMCs). Our in vivo µ-CT and flow cytometry data further showed that CQ administration improves bone health and preserves bone micro-architecture by markedly raising the proportion of anti-osteoclastogenic immune cells, such as Th1 (p < 0.05), Th2 (p < 0.05), Tregs (p < 0.05), and Bregs (p < 0.01), while concurrently lowering the osteoclastogenic Th17 cells in bone marrow, mesenteric lymph nodes, Peyer’s patches, and spleen in comparison to the control group. Serum cytokine analysis further supported the osteoprotective and immunoporotic potential of CQ, showing a significant increase in the levels of anti-osteoclastogenic cytokines (p < 0.05) (IFN-γ, IL-4, and IL-10) and a concurrent decrease in the levels of osteoclastogenic cytokines (p < 0.05) (TNF-α, IL-6, and IL-17). In conclusion, our data for the first time delineates the novel cellular and immunological mechanism of the osteoprotective potential of CQ under postmenopausal osteoporotic conditions. Keywords: Cissus quadrangularis, osteoporosis, immunoporosis, Th17, Tregs, Bregs

Author Biographies

Zaffar Azam, Translational Immunology, Osteoimmunology &amp; Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India

Methodology, Investigation, Writing – original draft

Leena Sapra, Translational Immunology, Osteoimmunology &amp; Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India

Methodology, Validation, Investigation, Writing – original draft, Writing – review & editing

Kalpana Baghel, Department of Zoology, Dr. Harisingh Gour Vishwavidyalaya (Central University), Sagar 470003, India

Resources

Niharika Sinha, Drug Development Laboratory, School of Vocational Studies and Applied Sciences, Gautam Buddha University, Greater Noida 201312, India

Methodology

Rajesh Gupta, Drug Development Laboratory, School of Vocational Studies and Applied Sciences, Gautam Buddha University, Greater Noida 201312, India

Methodology

Vandana Soni, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar 470003, India

Methodology

Chaman Saini, Translational Immunology, Osteoimmunology &amp; Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India

Methodology

Rupesh Srivastava, Translational Immunology, Osteoimmunology &amp; Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India

Conceptualization, Methodology, Formal analysis, Investigation, Resources, Writing – original draft, Visualization, Supervision, Project administration, Funding acquisition

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