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Abstract Title:

Melatonin rescues osteoporosis by upregulating BMMSCs' osteogenic ability but suppressing BMMSC-mediated osteoclastogenesis via MT2-inactivated NF-

Abstract Source:

Br J Pharmacol. 2020 Jan 3. Epub 2020 Jan 3. PMID: 31900938

Abstract Author(s):

Yi Zhou, Chaowei Wang, Jinyan Si, Baixiang Wang, Denghui Zhang, Ding Ding, Jian Zhang, Huiming Wang

Article Affiliation:

Yi Zhou

Abstract:

BACKGROUND AND PURPOSE: Melatonin is a neurohormone involved in many biological activities, especially bone homeostasis. However, how melatonin directs bone remodelling and the role of bone marrow mesenchymal stem cells (BMMSCs) in the regulating melatonin-mediated bone formation-resorption balance remain undefined.

EXPERIMENTAL APPROACH: Osteoporosis models were established, and bone tissue and serum were collected to test the effects of melatonin on bone homeostasis. Melatonin receptors (MT receptors) were knocked down, the NF-κB signalling pathway and receptor activator of nuclear factor-κB ligand (RANKL) expression were investigated, and communication between BMMSCs and osteoclasts was detected with direct-contact or indirect-contact system.

KEY RESULTS: Bone loss and microstructure disorder in mice were profoundly reversed after melatonin treatment, as an integrated result of anabolic and anti-resorptive effects. In vitro, a low physiological melatonin concentration selectively promoted the BMMSCs' osteogenic lineage commitment and extracellular mineralization, but had no impact on extracellular matrix synthesis. After MT knockdown, especially MT2 knockdown, the positive effects of melatonin on osteogenesis were attenuated. The canonical NF-κB signalling pathway was the first discovered downstream signalling pathway after MT receptor activation and was found to be downregulated by melatonin during osteogenesis. Melatonin suppressed BMMSC-mediated osteoclastogenesis by inhibiting RANKL production in BMMSCs, and this effect only occurred when BMMSCs and osteoclast precursors were co-cultured in an indirect-contact manner.

CONCLUSION AND IMPLICATIONS: Our work suggests that melatonin plays a crucial role in bone balance, significantly accelerates the osteogenic differentiation of BMMSCs by suppressing the MT2-dependent NF-κB signalling pathway, and downregulates osteoclastogenesis via RANKL paracrine secretion.

Study Type : Animal Study
Additional Links
Pharmacological Actions : Osteogenic : CK(52) : AC(12)

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