Morinda officinalis polysaccharide enable suppression of osteoclastic differentiation by exosomes derived from rat mesenchymal stem cells

Abstract

Context Morinda officinalis F.C. How. (MO) (Rubiaceae) can strengthen bone function. Objective To examine the functional mechanism and effect of MO polysaccharides (MOPs) in rats with glucocorticoid-induced osteoporosis (GIOP). Materials and methods Rats with GIOP were treated with 5, 15 or 45 mL/kg of MOP [ n = 15 for each dose, intraperitoneal (i.p.) injection every other day for 8 weeks]. The body weight of rats and histomorphology of bone tissues were examined. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exo) were collected and identified. Bone marrow-derived macrophages (BMMs) were induced to differentiate into osteoclasts and treated with BMSC-Exo for in vitro studies. Results MOP reduced the body weight (5, 15, or 45 mg/kg MOP vs. phosphate-buffered saline: 8%, 15% and 25%, p < 0.01), elevated the bone volume to tissue volume (BV/TV), mean trabecular thickness (Tb.Th), mean trabecular number (Tb.N) and mean connectivity density (Conn.D) (40–86%, p < 0.01), decreased the mean trabecular separation/spacing (Tb.Sp) (22–37%, p < 0.01), increased the cortical bone continuity (35–90%, p < 0.01) and elevated RUNX family transcription factor 2 and RANK levels (5–12%, p < 0.01), but suppressed matrix metallopeptidase 9 and cathepsin K levels (9–20%, p < 0.01) in femur tissues. BMSC-Exo from MOP-treated rats (MOP-Exo) suppressed osteoclastic differentiation and proliferation of BMMs. The downregulation of microRNA-101-3p (miR-101-3p) or the upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2) blocked the functions of MOP-Exo. Discussion and conclusions MOP inhibits osteoclastic differentiation and could potentially be used for osteoporosis management. This suppression may be enhanced by the upregulation of miR-101-3p or the inhibition of PTGS2.

Wen-Shen-Tong-Luo-Zhi-Tong Decoction regulates bone–fat balance in osteoporosis by adipocyte-derived exosomes

“…Active ingredients of Chinese herbs such as Morinda officinalis F. C. How (Rubiaceae), enable suppression of osteoclastic differentiation by exosomes derived from rat mesenchymal stem cells (Wu et al. 2022 ). In this study, we first extracted adipocyte-derived exosomes by ultracentrifugation and successfully identified them via transmission electron microscopy (TEM), NTA and western blotting (WB).…”

The Potential of Exosomes for Osteoporosis Treatment: A Review

“…The osteoclastic differentiation and proliferation of BMMs may be effectively reduced by treating BMSC-Exo from MOP-treated GIOP rats (MOP-Exo) via upregulating prostaglandin-endoperoxide synthase 2 (PTGS2) and downregulating miR-101-3p. 78 Bovine colostrum-derived exosomes inhibited osteoclast differentiation in Raw264.7 cells. 79 In mice with glucocorticoid-induced osteoporosis, oral administration of exosomes produced from bovine colostrum for two months markedly increased bone mineral density via improvement in the composition of gut microbiota.…”

“… 77 Additionally, a recent study demonstrated that MOP therapy helped alleviate the symptoms of osteoporosis in rats with GIOP by promoting osteoblastic differentiation and suppressing osteoclastic differentiation. 78 Osteoclast differentiation was induced in BMMs. Osteoclastic differentiation and the development of BMMs generated by RANKL were dramatically enhanced when BMSC-Exo isolated from GIOP rats were treated.…”

Mechanisms by which kidney-tonifying Chinese herbs inhibit osteoclastogenesis: Emphasis on immune cells

“…Yin, (2017) It protected bone loss and biomechanical dysfunction in OVX-rats and had antiosteoporosis activity through OPG/RANK/RANKL ( Zhang et al 2020 ; Peng and Zhong 2020 ), while inhibiting OC differentiation through the exosomes of mesenchymal stem cells, which was closely related to the expression of PTGS2 and miR-101-3p. Wu et al (2022c) Bajijiasu and Rubiadin-1-mrthyl ether inhibited the expression of OC-specific genes induced by RANKL through the NF-κB pathway to inhibit OC generation and function and treat osteolytic bone diseases. Hong et al (2017) ; He et al (2018) .…”