Comparative Study of DHA with Different Molecular Forms for Ameliorating Osteoporosis by Promoting Chondrocyte-to-Osteoblast Transdifferentiation in the Growth Plate of Ovariectomized Mice

Abstract

Osteoblasts play a key role in bone remodeling. Recent studies have reported that some hypertrophic chondrocytes co-expressing collagen I(Col I) and collagen X (ColX) could directly transdifferentiate into osteoblasts during endochondral ossification. However, whether nutrition intervention is beneficial to this transformation to improve osteoporosis (OP) remains unknown. In this study, ovariectomy (OVX)-induced OP mice were orally administered with docosahexaenoic acid (DHA) in different molecular forms for 13 weeks. The results showed that both DHA-triglyceride (DHA-TG) and DHA-phosphatidylcholine (DHA-PC) increased the bone mineral density and bone mineral apposition rate in ovariectomized mice, while DHA-ethyl esters (DHA-EE) had little effect. Interestingly, we found that both DHA-PC and DHA-TG increased the height of the growth plate, mainly increasing the number of hypertrophic chondrocytes. Further investigation by simultaneously labeling ColX and ColI indicated that DHA-PC and DHA-TG promoted the number of chondrocyte-transdifferentiated osteoblasts in the growth plate close to the diaphysis, in which DHA-PC performed better than DHA-TG. Apoptosis was not the only fate of hypertrophic chondrocytes. Western blot results showed that both DHA-TG and DHA-PC downregulated the Bax and cleaved-caspase3 expression and upregulated Bcl-2 expression in the growth plate, suggesting that chondrocyte apoptosis is inhibited. Runx2, the key regulator of chondrocyte-to-osteoblast transdifferentiation, was significantly increased by DHA-TG and DHA-PC, while DHA-EE had no effect on the above indicators. To our best knowledge, this is the first report that both DHA-PC and DHA-TG enhanced bone formation via promoting the chondrocyte-to-osteoblast transdifferentiation in the growth plate, contributing to the amelioration of OP. These activities depend on the molecular forms of DHA and their bioavailabilities. Our results provide guidance for the application of fish oil for bone health.

Cellular direct conversion by cell penetrable OCT4-30Kc19 protein and BMP4 growth factor

“…So, it opens the possibility of cell therapy that can transform the whole tissue into desired cell types. Direct conversion at the tissue level could alleviate impaired balances between adipogenesis and osteogenesis occurred in osteoporosis [ 74 – 76 ], by targeting increased portion of adipose tissue in the bone marrow.…”

Comparative study of holothurin A and echinoside A on inhibiting the high bone turnover via downregulating PI3K/AKT/β-catenin and OPG/RANKL/NF-κB signaling in ovariectomized mice

“…Quantitative real-time PCR was performed as described previously. 4 Total RNA was extracted from femur tissue with TRIzol reagent. The RNA (1 μg) of each sample was reverse transcribed into cDNA.…”

“…For example, Zhang et al found that DHA separated from squid roe attenuated osteoporosis in ovariectomized mice. 4 Xia et al reported that supplementation with phosphorylated peptides from Antarctic krill prevented bone loss in ovariectomized mice. 5 It is generally accepted that adult bone mass is maintained by a balance of the activities of osteoblasts and osteoclasts.…”

“…For example, Zhang et al found that DHA separated from squid roe attenuated osteoporosis in ovariectomized mice. 4 Xia et al reported that supplementation with phosphorylated peptides from Antarctic krill prevented bone loss in ovariectomized mice. 5…”

Mesenchymal Stem Cell-Derived Extracellular Vesicle: A Promising Alternative Therapy for Osteoporosis

“…Osteoporosis, a metabolic skeletal disorder that results from the imbalance between bone formation and bone resorption, generally occurs in postmenopausal women and older people [ 1 ]. The process of bone remodeling is participated by mainly osteoclasts and osteoblasts, together with other cells including osteocytes, bone lining cells, monocytes, chondrocytes, hematopoietic stem cells, and mesenchymal stem cells (MSCs) [ 2 , 3 , 4 ]. Owing to the complicated pathology and uninhibited signaling pathway of osteoporosis, the development of medications is floundering.…”