Low-molecular-weight estrogenic phytoprotein suppresses osteoporosis development through positive modulation of skeletal estrogen receptors

Age-related osteoporosis is a metabolic skeletal disorder caused by estrogen deficiency in postmenopausal women.Prolonged use of anti-osteoporotic drugs such as bisphosphonates and FDA-approved anti-resorptive selective estrogen receptor modulators(SERMs)has been associated with various clinical drawbacks.We recently discovered a low-molecular-weight biocompatible and osteoanabolic phytoprotein,called HKUOT-S2 protein(32 kDa),from Dioscorea opposita Thunb that can accelerate bone defect healing.Here,we demonstrated that the HKUOT-S2 protein treatment can enhance osteoblasts-induced ossification and suppress osteoporosis development by upregulating skeletal estrogen receptors(ERs)ERα,ERβ,and GPR30 expressions in vivo.Also,HKUOT-S2 protein estrogenic activities promoted hMSCs-osteoblasts differentiation and functions by increasing osteogenic markers,ALP,and RUNX2 expressions,ALP activity,and osteoblast biomineralization in vitro.Fulvestrant treatment impaired the HKUOT-S2 protein-induced ERs expressions,osteoblasts differentiation,and functions.Finally,we demonstrated that the HKUOT-S2 protein could bind to ERs to exert osteogenic and osteoanabolic properties.Our results showed that the biocompatible HKUOT-S2 protein can exert estrogenic and osteoanabolic properties by positively modulating skeletal estrogen receptor signaling to promote ossification and suppress osteoporosis.Currently,there is no or limited data if any,on osteoanabolic SERMs.The HKUOT-S2 protein can be applied as a new osteoanabolic SERM for osteoporosis treatment.

EFFECTS OF PARATHYROID HORMONE AND ESTRADIOL ON PROLIFERATION AND FUNCTION OF HUMAN OSTEOBLASTS FROM FETAL LONG BONE AN IN VITRO STUDY

The effect of parathyroid hormone (PTH) (0.01 nM-10 nM) and 17 -estradiol (E2, 1 nmol-10 nM) alone or in combination on 3H thymidine incorporation, alkaline phosphatase and adenylate cyclase activities were investigated in human fetal osteoblasts using serum-free monolayer primary cultures. The results showed that PTH inhibited cell proliferation while E, promoted it. On alkaline phosphatase activity, PTH showed a complex results while E, were slightly inhibitory. PHT-E2 combination suggested that E2 could alter the effect of PTH alone, also potentiated the anabolic and antagonize the catabolic effects of PTH on bone formation.

Immunomodulation and osseointegration activities of Na_(2)TiO_(3) nanorods-arrayed coatings doped with different Sr content

To endow Ti-based orthopedic implants immunomodulatory capability and thus enhanced osseointegration,different amounts of Sr are doped in Na_(2)TiO_(3) nanorods in the arrays with identical nanotopographic parameters(rod diameter,length and inter-rod spacing)by substitution of Na^(+) using hydrothermal treatment.The obtained arrays are denoted as STSr2,STSr4,and STSr7,where the arabic numbers indicate the incorporating amounts of Sr in Na_(2)TiO_(3).The modulation effects of the Sr-doped nanorods arrays on macrophage polarization and osteogenetic functions of osteoblasts are investigated,together with the array without Sr(ST).Moreover,osseointegration of these arrays are also assayed in rat femoral condyles.Sr-doped nanorods arrays accelerate M1(pro-inflammatory phenotype)-to-M2(anti-inflammatory phenotype)transformation of the adhered macrophages,enhancing secretion of pro-osteogenetic cytokines and growth factors(TGF-β1 and BMP2),moreover,the Sr doped arrays directly enhance osteogenetic functions of osteoblasts.The enhancement of paracrine of M2 macrophages and osteogenetic function of osteoblasts is promoted with the increase of Sr incorporating amounts.Consequently,Sr doped arrays show significantly enhanced osseointegration in vivo compared to ST,and STSr7 exhibits the best performance.Our work sheds a new light on the design of surface chemical components and structures for orthopedic implants to enhance their osseointegration.