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Sclerostin (Sost) is a negative regulator of bone formation and blocking its function via antibodies has shown great therapeutic promise by increasing both bone mass in humans and animal models. Sclerostin deletion in Sost KO mice (Sost-/- ) causes high bone mass (HBM) similar to sclerosteosis patients. Sost-/- mice have been shown to display an up to 300% increase in bone volume/total volume (BV/TV), relative to age-matched controls. It has been postulated that the main source of skeletal sclerostin is the osteocyte. To understand the cell-type specific contributions to the HBM phenotype described in Sost-/- mice, as well as to address the endocrine and paracrine mode of action of sclerostin, we examined the skeletal phenotypes of conditional Sost loss-of-function (SostiCOIN/iCOIN ) mice with specific deletions in (1) the limb mesenchyme (Prx1-Cre; targets osteoprogenitors and their progeny); (2) midstage osteoblasts and their progenitors (Col1-Cre); (3) mature osteocytes (Dmp1-Cre); and (4) hypertrophic chondrocytes and their progenitors (ColX-Cre). All conditional alleles resulted in significant increases in bone mass in trabecular bone in both the femur and lumbar vertebrae, but only Prx1-Cre deletion fully recapitulated the amplitude of the HBM phenotype in the appendicular skeleton and the B-cell defect described in the global KO. Despite WT expression of Sost in the axial skeleton of Prx1-Cre deleted mice, these mice also had a significant increase in bone mass in the vertebrae, but the sclerostin released in circulation by the axial skeleton did not affect bone parameters in the appendicular skeleton. Also, both Col1 and Dmp1 deletion resulted in a similar 80% significant increase in trabecular bone mass, but only Col1 and Prx1 deletion resulted in a significant increase in cortical thickness. We conclude that several cell types within the Prx1-osteoprogenitor-derived lineages contribute significant amounts of sclerostin protein to the paracrine pool of Sost in bone. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

The new Penal Code in 2009 was an opportunity for Timor-Leste to allow some legal grounds for abortion, which was highly restricted under Indonesian rule. Public debate was contentious before ratification of the new code, which allowed abortion to save a woman's life and health. A month later, 13 amendments to the code were passed, highly restricting abortion again. This paper describes the socio-legal context of unsafe abortion in Timor-Leste, based on research in 2006-08 on national laws and policies and interviews with legal professionals, police, doctors and midwives, and community-based focus group discussions. Data on unsafe abortions in Timor-Leste are rarely recorded. A small number of cases of abortion and infanticide are reported but are rarely prosecuted, due to deficiencies in evidence and procedure. While there are voices supporting law reform, the Roman Catholic church heavily influences public policy and opinion. Professional views on when abortion should be legal varied, but in the community people believed that saving women's lives was paramount and came before the law. The revised Penal Code is insufficient to reduce unsafe abortion and maternal mortality. Change will be slow, but access to safe abortion and modern contraception are crucial to women's ability to participate fully as citizens in Timor-Leste.