Abstract
BackgroundOsseointegration is dependent on the implant surface, surrounding bone quality, and the systemic host environment, which can differ in male and female patients. Titanium (Ti) implants with microstructured surfaces exhibit greater pullout strength when compared to smooth-surfaced implants and exhibit enhanced osteogenic cellular responses in vitro. Previous studies showed that 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] has a greater effect on rat osteoblast differentiation on microstructured Ti compared to smooth Ti surfaces and tissue culture polystyrene (TCPS). The stimulatory effect of 17β-estradiol (E2) on differentiation is observed in female osteoblasts on micro-rough Ti, but it is not known if male osteoblasts behave similarly in response to E2 and microtopography. This study assessed whether human male and female osteoblasts exhibit sex-specific differences in response to E2 and 1α,25(OH)2D3 when cultured on microstructured Ti surfaces.MethodsOsteoblasts from three male and three female human donors were cultured on Ti discs with varying surface profiles: a smooth pretreatment (PT), a coarse grit-blasted/acid-etched (SLA), and an SLA surface having undergone modification in a nitrogen environment and stored in saline to maintain hydrophilicity (modSLA). Cells cultured on these surfaces were treated with E2 or 1α,25(OH)2D3.ResultsMale and female human osteoblasts responded similarly to microstructure although there were donor-specific differences; cell number decreased, and osteocalcin (OCN), osteoprotegerin (OPG), and latent and active transforming growth factor 1 increased on SLA and modSLA compared to TCPS. Female osteoblasts had higher alkaline phosphatase activity and OCN production than male counterparts but produced less OPG. Both sexes responded similarly to 1α,25(OH)2D3. E2 treatment reduced cell number and increased osteoblast differentiation and factor production only in female cells.ConclusionsMale and female human osteoblasts respond similarly to microstructure and 1α,25(OH)2D3 but exhibit sexual dimorphism in substrate-dependent responses to E2. E2 affected female osteoblasts, suggesting that signaling is sex-specific and surface-dependent. Donor osteoblasts varied in response, demonstrating the need to test multiple donors when examining human samples. Understanding how male and female cells respond to orthopedic biomaterials will enable greater predictability post-implantation as well as therapies that are more patient-specific.
Highlights
Osseointegration is dependent on the implant surface, surrounding bone quality, and the systemic host environment, which can differ in male and female patients
Female cells did not exhibit a general Ti-dependent reduction in cell number compared to tissue culture polystyrene (TCPS), but female cell numbers were reduced on SLA and modSLA, and the effect was comparable to that seen in male cells
Activity was increased by 100% on SLA and modSLA compared to TCPS and PT for both sexes, but the magnitude of the effect was much greater in the female cell cultures
Summary
Osseointegration is dependent on the implant surface, surrounding bone quality, and the systemic host environment, which can differ in male and female patients. Previous studies showed that 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] has a greater effect on rat osteoblast differentiation on microstructured Ti compared to smooth Ti surfaces and tissue culture polystyrene (TCPS). This study assessed whether human male and female osteoblasts exhibit sex-specific differences in response to E2 and 1α,25(OH)2D3 when cultured on microstructured Ti surfaces. Extracellular matrix proteins called small integrin binding, N-linked glycoproteins (SIBLING proteins), are encoded on the X-chromosome Mutations in these genes are expressed asymmetrically between males and females, since males inherit only one copy of these genes, and conditions resulting from these gene mutations are more common in boys [3]. Adipose stem cells (ASCs) from post-menopausal females exhibit a greater preference for lineage commitment to osteoblasts than aged-matched male ASCs [5]
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