Temporal expression of PTHrP during endochondral bone formation in mouse and intramembranous bone formation in an in vivo rabbit model

Kartsogiannis, Vicky; Moseley, Jane M.; McKelvie, B.; Chou, S.T.; Hards, D.K.; Ng, KW; Martin, T. J.; Zhou, Hong

doi:10.1016/s8756-3282(97)00180-4

Cited by 99 publications

(77 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, although the patterns of expression of PTHrP in the developing limb and the growing antler are similar (e.g. expression in perichondrium), some distinct differences can be observed (Kartsogiannis et al 1997;Farquharson et al 2001;Medill et al 2001;Nakase et al 2001;Kindblom et al 2002). The most obvious difference is the lack of PTHrP expression in differentiated antler chondrocytes.…”

Section: Local Factors That Regulate Antler Regenerationmentioning

confidence: 97%

Exploring the mechanisms regulating regeneration of deer antlers

Price

Allen

2004

Phil. Trans. R. Soc. Lond. B

110

View full text Add to dashboard Cite

Deer antlers are the only mammalian appendages capable of repeated rounds of regeneration; every year they are shed and regrow from a blastema into large branched structures of cartilage and bone that are used for fighting and display. Longitudinal growth is by a process of modified endochondral ossification and in some species this can exceed 2 cm per day, representing the fastest rate of organ growth in the animal kingdom. However, despite their value as a unique model of mammalian regeneration the underlying mechanisms remain poorly understood. We review what is currently known about the local and systemic regulation of antler regeneration and some of the many unsolved questions of antler physiology are discussed. Molecules that we have identified as having potentially important local roles in antlers include parathyroid hormone-related peptide and retinoic acid (RA). Both are present in the blastema and in the rapidly growing antler where they regulate the differentiation of chondrocytes, osteoblasts and osteoclasts in vitro. Recent studies have shown that blockade of RA signalling can alter cellular differentiation in the blastema in vivo. The trigger that regulates the expression of these local signals is likely to be changing levels of sex steroids because the process of antler regeneration is linked to the reproductive cycle. The natural assumption has been that the most important hormone is testosterone, however, at a cellular level oestrogen may be a more significant regulator. Our data suggest that exogenous oestrogen acts as a 'brake', inhibiting the proliferation of progenitor cells in the antler tip while stimulating their differentiation, thus inhibiting continued growth. Deciphering the mechanism(s) by which sex steroids regulate cell-cycle progression and cellular differentiation in antlers may help to address why regeneration is limited in other mammalian tissues.

show abstract

Section: Local Factors That Regulate Antler Regenerationmentioning

confidence: 97%

Exploring the mechanisms regulating regeneration of deer antlers

Price

Allen

2004

Phil. Trans. R. Soc. Lond. B

110

View full text Add to dashboard Cite

show abstract

“…We had expected to identify lacZ expression in osteoblasts [34] and perhaps osteoclasts [35] but found no clear β gal activity in these cells in our initial survey [13]. We have now looked at this question more carefully, using the more specific heat-inactivation protocol to score exogenous galactosidase activity [20], looking at an extensive number of sites in the PTHrPlacZ CD-1 mice, and also after inbreeding the PTHrP-lacZ allele into a C57Bl/6 background.…”

Section: Bone Cellsmentioning

confidence: 99%

Mechanical regulation of PTHrP expression in entheses

Chen¹,

Macica²,

Nasiri³

et al. 2007

Bone

View full text Add to dashboard Cite

The PTHrP gene is expressed in the periosteum and in tendon and ligament insertion sites in a PTHrPlacZ knockin reporter mouse. Here, we present a more detailed histological evaluation of PTHrP expression in these sites and study the effects of mechanical force on PTHrP expression in selected sites. We studied the periosteum and selected entheses by histological, histochemical, and in situ hybridization histochemical techniques, and tendons or ligaments were unloaded by tail suspension or surgical transection. In the periosteum, PTHrP is expressed in the fibrous layer and the type 1 PTH/PTHrP receptor (PTH1R) in the subjacent cambial layer. PTHrP has distinct temporospatial patterns of expression in the periosteum, one hot spot being the metaphyseal periosteum in growing animals. PTHrP is also strongly expressed in a number of fibrous insertion sites. In the tibia these include the insertions of the medial collateral ligament (MCL) and the semimembraneosus (SM). In young animals, the MCL and SM sites display a combination of underlying osteoblastic and osteoclastic activities that may be associated with the migration of these entheses during linear growth. Unloading the MCL and SM by tail suspension or surgical transection leads to a marked decrease in PTHrP/lacZ expression and a rapid disappearance of the subjacent osteoblastic population. We have not been able to identify PTHrP-lacZ in any internal bone cell population in the PTHrP-lacZ knockin mouse in either a CD-1 or C57Bl/6 genetic background.In conclusion, we have identified PTHrP expression in surface structures that connect skeletal elements to each other and to surrounding muscle but not in intrinsic internal bone cell populations. In these surface sites, mechanical force seems to be an important regulator of PTHrP expression. In selected sites and/or at specific times, PTHrP may influence the recruitment and/or activities of underlying bone cell populations.

show abstract

“…(24,25) This includes bone, where it is produced by cells within the osteoblast lineage. (26)(27)(28)(29) PTHrP homology with PTH is restricted to the amino-terminal region, equipping them to act with equivalent potencies on the common receptor, PTHR1. (30,31) PTHrP has other actions mediated by unique regions within the molecule beyond the amino-terminal region that is homologous with PTH.…”

Section: Anabolic Therapy With Parathyroid Hormone (Pth) and Abaloparmentioning

confidence: 99%

Abaloparatide Is an Anabolic, but Does It Spare Resorption?

Martın

Seeman

2016

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

L ongevity is increasing the burden of fractures. Although antiresorptive therapy slows remodeling, it does not prevent or repair microstructural deterioration. The challenge is to reconstruct the skeleton. The more advanced the patient's age, the more likely that microstructural deterioration is severe and so the more rational the choice of an anabolic agent as first-line therapy. PTH(1-34) (teriparatide) reduces vertebral and nonvertebral fracture risk, in part, by increasing bone matrix volume. Abaloparatide has also recently been reported to reduce morphometric vertebral fracture risk (1,2) and is thus a most welcome addition to the therapeutics of bone fragility. Abaloparatide is claimed to produce its anabolic effect with a much lesser effect on bone resorption than occurs with teriparatide. In this Commentary, we query the latter proposition, which we suggest contains two misconceptions: first, that with teriparatide treatment an anabolic window exists during which bone formation predominates but then is offset by bone resorption, which follows later, and second that less bone resorption occurs with abaloparatide, leaving the "window" open longer and allowing more bone formation. Anabolic Therapy With Parathyroid Hormone (PTH) and AbaloparatideTo understand the fallacies in these two notions, the mythical anabolic window and the purported lesser resorptive effect of abaloparatide, it is necessary first to discuss the mechanisms of action of PTH. The idea that intermittent injection of PTH might promote bone formation was proposed more than 80 years ago by Albright (3) and shown in rats by Selye.Progress was slow, with no attempt to study PTH treatment clinically until the 1970s. The first clinical trial was published in 2001 (5) and was stopped after 18 months because of a toxicity study that showed dose-dependent development of osteosarcoma in rats treated throughout their lives. (6) With the total number of subjects in the clinical trial reduced to 1600 and the duration of treatment being only 18 months, no potential antihip fracture efficacy could be demonstrated, but vertebral and nonvertebral fracture risk was reduced and bone mineral density (BMD) increased.The efficacy of teriparatide as an anabolic therapy depends on intermittent injections, each achieving a sharp peak of PTH in the blood.(7) When teriparatide therapy is begun, circulating bone formation markers increase rapidly, with a delayed appearance of resorption markers, giving rise to the concept of the "anabolic window." (8,9) This was based on the idea that the initial period of increased anabolic markers reflects an early period of bone formation relatively "unopposed" by resorption but then superseded by subsequent increases in bone resorption. This theory was not based on histomorphometric evidence of changing volumes of bone formation and resorption but rather inferred from finding an early increase in bone "formation" markers, followed by a later increase in bone "resorption" markers.Abaloparatide is a 34-amino acid peptide acting u...

show abstract

Temporal expression of PTHrP during endochondral bone formation in mouse and intramembranous bone formation in an in vivo rabbit model

Cited by 99 publications

References 34 publications

Exploring the mechanisms regulating regeneration of deer antlers

Exploring the mechanisms regulating regeneration of deer antlers

Mechanical regulation of PTHrP expression in entheses

Abaloparatide Is an Anabolic, but Does It Spare Resorption?

Contact Info

Product

Resources

About