Angiotensin II type 2 receptor blockade increases bone mass.

Abstract

On page 51726, we misleadingly stated that the central acidic domain in Dsl1p is essential for viability. Evidence for this was presented in Fig. 3C. This figure shows that a mutant carrying two Trp-to-Ala replacements in this region did not support growth of a dsl1 deletion mutant. However, we recently created a GAL-regulated TAP-tagged version of DSL1 carrying five Trp-to-Ala substitutions in this region to use as a negative control in pulldown experiments. Surprisingly, this mutant complemented the dsl1 knock-out. Even a single-copy untagged version of this allele could replace the wild-type gene. However, these cells grow poorly at all temperatures tested and show phenotypes similar to those of Dsl1p-depleted cells.Sequencing showed that the plasmid used for the growth assay in our previous work contained a C-terminal truncation in addition to the Trp-to-Ala substitutions at positions 413 and 455. A mutant clone with an intact C terminus supported growth of a dsl1 deletion mutant.Our recent data are still consistent with the notion that the outer tryptophan motifs in the acidic domain of Dsl1p ( ADDITIONS AND CORRECTIONS This paper is available online at www.jbc.orgWe suggest that subscribers photocopy these corrections and insert the photocopies in the original publication at the location of the original article. Authors are urged to introduce these corrections into any reprints they distribute. Secondary (abstract) services are urged to carry notice of these corrections as prominently as they carried the original abstracts.

Influences of Treatment with Amlodipine and Valsartan on Bone Turnover Markers and OPG/RANKL/RANK System in Newly Diagnosed Hypertensive Adults; Which is more Beneficial?

“…Telmisartan treatment was shown to improve rosiglitazone-induced bone loss in ovariectomized spontaneously hypertensive rats (25). Another ARB, losartan, enhanced bone mass in adult mice and this effect was based on the stimulation of bone formation and the inhibition of bone resorption (14). On the contrary, no effect of ARBs has been found on bone loss in several other animal studies (7,12,26).…”

“…Beyond RAS inhibition, identifi cation of accompanying mechanisms has motivated studies evaluating the relationship between blockade of this system and modifi cation of bone density (12)(13)(14). Valsartan, a well known and widely used ARB, displayed no effect on bone transforming growth factor-beta1 which is known as osteoporosis tendency factor (15).…”

“…Because, again in animals, angiotensin II was demonstrated to accelerate osteoporosis by activating osteoclasts, while this effect was abolished by an ARB administration (13). Moreover, increase in bone mass was demonstrated after treatment with ARBs, which was linked both to enhanced osteoblastic and suppressed osteoclastic activity (14). Nevertheless, angiotensin II was also shown to cause proliferation of osteoblasts (16), suggesting that blockage of this enzyme may result in impaired bone formation in vivo.…”

Renin Inhibition Improves Ovariectomy-Induced Osteoporosis of Lumbar Vertebra in Mice

“…8) Recent studies showed that the components of RAS, such as renin, ACE, and ANG II receptors, are also expressed in the local milieu of bone. 9,10) Functional studies revealed that ANG II could stimulate the differentiation and activity of osteoclasts in vivo 11) and in vitro, 12) and aggravate the loss of bone minerals in rats with osteoporosis induced by estrogen deficiency, 11) furthermore, the ANG II type 1 receptor knockout mice showed high bone mass. 13) In addition, we recently demonstrated that the local RAS in bone was involved in age-related osteoporosis of aging mice, 14) bone deteriorations of mice with either obstructive nephropathy 15) or type 1 diabetes, 16) and others elucidated the involvement of skeletal RAS in the process of fracture healing in a mouse femur fracture model.…”

“…2) The experimental studies have showed the beneficial effects of ACEI and ARB on maintaining bone health of ovariectomized (OVX) rats 11,18,19) and mice, 10,20) an animal model mimicking postmenopausal osteoporosis due to the decline of circulating estrogen level. While, given renin is the rate-limiting enzyme of the RAS, whether the RAS inhibition by inhibiting renin activity could show beneficial effects on postmenopausal osteoporosis is not known.…”