Postmenopausal osteoporosis, a global public health problem, has for decades been attributed solely to declining estrogen levels. Although FSH levels rise sharply in parallel, a direct effect of FSH on the skeleton has never been explored. We show that FSH is required for hypogonadal bone loss. Neither FSHbeta nor FSH receptor (FSHR) null mice have bone loss despite severe hypogonadism. Bone mass is increased and osteoclastic resorption is decreased in haploinsufficient FSHbeta+/- mice with normal ovarian function, suggesting that the skeletal action of FSH is estrogen independent. Osteoclasts and their precursors possess G(i2alpha)-coupled FSHRs that activate MEK/Erk, NF-kappaB, and Akt to result in enhanced osteoclast formation and function. We suggest that high circulating FSH causes hypogonadal bone loss.

This study aims to explore the fundamental surface characteristics of polydopamine (pDA)-coated hydrophobic polymer films. A poly(vinylidene fluoride) (PVDF) film was surface modified by dip coating in an aqueous solution of dopamine on the basis of its self-polymerization and strong adhesion feature. The self-polymerization and deposition rates of dopamine on film surfaces increased with increasing temperature as evaluated by both spectroscopic ellipsometry and scanning electronic microscopy (SEM). Changes in the surface morphologies of pDA-coated films as well as the size and shape of pDA particles in the solution were also investigated by SEM, atomic force microscopy (AFM), and transmission electron microscopy (TEM). The surface roughness and surface free energy of pDA-modified films were mainly affected by the reaction temperature and showed only a slight dependence on the reaction time and concentration of the dopamine solution. Additionally, three other typical hydrophobic polymer films of polytetrafluoroethylene (PTFE), poly(ethylene terephthalate) (PET), and polyimide (PI) were also modified by the same procedure. The lyophilicity (liquid affinity) and surface free energy of these polymer films were enhanced significantly after being coated with pDA, as were those of PVDF films. It is indicated that the deposition behavior of pDA is not strongly dependent on the nature of the substrates. This information provides us with not only a better understanding of biologically inspired surface chemistry for pDA coatings but also effective strategies for exploiting the properties of dopamine to create novel functional polymer materials.

Menopause is associated with bone loss and enhanced visceral adiposity. We have shown previously that a polyclonal antibody (Ab) to the β-subunit of the pituitary hormone Fsh increases bone mass in mice. Here, we report that this Ab sharply reduces adipose tissue in wild type mice, phenocopying genetic Fshr haploinsufficiency. The Ab also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue, and enhances thermogenesis. These actions result from the specific binding of Ab to Fshβ to block its action. Our studies uncover novel opportunities for co-treating obesity and osteoporosis.

In nonneuronopathic type 1 Gaucher disease (GD1), mutations in the glucocerebrosidase gene (GBA1) gene result in glucocerebrosidase deficiency and the accumulation of its substrate, glucocerebroside (GL-1), in the lysosomes of mononuclear phagocytes. This prevailing macrophage-centric view, however, does not explain emerging aspects of the disease, including malignancy, autoimmune disease, Parkinson disease, and osteoporosis. We conditionally deleted the GBA1 gene in hematopoietic and mesenchymal cell lineages using an Mx1 promoter. Although this mouse fully recapitulated human GD1, cytokine measurements, microarray analysis, and cellular immunophenotyping together revealed widespread dysfunction not only of macrophages, but also of thymic T cells, dendritic cells, and osteoblasts. The severe osteoporosis was caused by a defect in osteoblastic bone formation arising from an inhibitory effect of the accumulated lipids LysoGL-1 and GL-1 on protein kinase C. This study provides direct evidence for the involvement in GD1 of multiple cell lineages, suggesting that cells other than macrophages may be worthwhile therapeutic targets.