Increased bone formation byprevention of osteoblast apoptosis with parathyroid hormone

Robert L. Jilka, Robert S. Weinstein, Teresita Bellido, Paula Roberson, A. Michael Parfitt, Stavros C. Manolagas

Research output: Contribution to journalArticle

782 Citations (Scopus)

Abstract

The mass of regenerating tissues, such as bone, is critically dependent on the number of executive cells, which in turn is determined by the rate of replication of progenitors and the life-span of mature cells, reflecting the timing of death by apoptosis. Bone mass can be increased by intermittent parathyroid hormone (PTH) administration, but the mechanism of this phenomenon has remained unknown. We report that daily PTH injections in mice with either normal bone mass or osteopenia due to defective osteoblastogenesis increased bone formation without affecting the generation of new osteoblasts. Instead, PTH increased the life-span of mature osteoblasts by preventing their apoptosis - the fate of the majority of these cells under normal conditions. The antiapoptotic effect of PTH was sufficient to account for the increase in bone mass, and was confirmed in vitro using rodent and human osteoblasts and osteocytes. This evidence provides proof of the basic principle that the work performed by a cell population can be increased by suppression of apoptosis. Moreover, it suggests novel pharmacotherapeutic strategies for osteoporosis and, perhaps, other pathologic conditions in which tissue mass diminution has compromised functional integrity.

Original languageEnglish (US)
Pages (from-to)439-446
Number of pages8
JournalJournal of Clinical Investigation
Volume104
Issue number4
StatePublished - Aug 1999
Externally publishedYes

Fingerprint

Parathyroid Hormone
Osteoblasts
Osteogenesis
Apoptosis
Bone and Bones
Osteocytes
Metabolic Bone Diseases
Osteoporosis
Rodentia
Cell Count
Injections
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Jilka, R. L., Weinstein, R. S., Bellido, T., Roberson, P., Parfitt, A. M., & Manolagas, S. C. (1999). Increased bone formation byprevention of osteoblast apoptosis with parathyroid hormone. Journal of Clinical Investigation, 104(4), 439-446.

Increased bone formation byprevention of osteoblast apoptosis with parathyroid hormone. / Jilka, Robert L.; Weinstein, Robert S.; Bellido, Teresita; Roberson, Paula; Parfitt, A. Michael; Manolagas, Stavros C.

In: Journal of Clinical Investigation, Vol. 104, No. 4, 08.1999, p. 439-446.

Research output: Contribution to journalArticle

Jilka, RL, Weinstein, RS, Bellido, T, Roberson, P, Parfitt, AM & Manolagas, SC 1999, 'Increased bone formation byprevention of osteoblast apoptosis with parathyroid hormone', Journal of Clinical Investigation, vol. 104, no. 4, pp. 439-446.
Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC. Increased bone formation byprevention of osteoblast apoptosis with parathyroid hormone. Journal of Clinical Investigation. 1999 Aug;104(4):439-446.
Jilka, Robert L. ; Weinstein, Robert S. ; Bellido, Teresita ; Roberson, Paula ; Parfitt, A. Michael ; Manolagas, Stavros C. / Increased bone formation byprevention of osteoblast apoptosis with parathyroid hormone. In: Journal of Clinical Investigation. 1999 ; Vol. 104, No. 4. pp. 439-446.
@article{bbfa236b37c347df938b1edc1cd66766,
title = "Increased bone formation byprevention of osteoblast apoptosis with parathyroid hormone",
abstract = "The mass of regenerating tissues, such as bone, is critically dependent on the number of executive cells, which in turn is determined by the rate of replication of progenitors and the life-span of mature cells, reflecting the timing of death by apoptosis. Bone mass can be increased by intermittent parathyroid hormone (PTH) administration, but the mechanism of this phenomenon has remained unknown. We report that daily PTH injections in mice with either normal bone mass or osteopenia due to defective osteoblastogenesis increased bone formation without affecting the generation of new osteoblasts. Instead, PTH increased the life-span of mature osteoblasts by preventing their apoptosis - the fate of the majority of these cells under normal conditions. The antiapoptotic effect of PTH was sufficient to account for the increase in bone mass, and was confirmed in vitro using rodent and human osteoblasts and osteocytes. This evidence provides proof of the basic principle that the work performed by a cell population can be increased by suppression of apoptosis. Moreover, it suggests novel pharmacotherapeutic strategies for osteoporosis and, perhaps, other pathologic conditions in which tissue mass diminution has compromised functional integrity.",
author = "Jilka, {Robert L.} and Weinstein, {Robert S.} and Teresita Bellido and Paula Roberson and Parfitt, {A. Michael} and Manolagas, {Stavros C.}",
year = "1999",
month = "8",
language = "English (US)",
volume = "104",
pages = "439--446",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "4",

}

TY - JOUR

T1 - Increased bone formation byprevention of osteoblast apoptosis with parathyroid hormone

AU - Jilka, Robert L.

AU - Weinstein, Robert S.

AU - Bellido, Teresita

AU - Roberson, Paula

AU - Parfitt, A. Michael

AU - Manolagas, Stavros C.

PY - 1999/8

Y1 - 1999/8

N2 - The mass of regenerating tissues, such as bone, is critically dependent on the number of executive cells, which in turn is determined by the rate of replication of progenitors and the life-span of mature cells, reflecting the timing of death by apoptosis. Bone mass can be increased by intermittent parathyroid hormone (PTH) administration, but the mechanism of this phenomenon has remained unknown. We report that daily PTH injections in mice with either normal bone mass or osteopenia due to defective osteoblastogenesis increased bone formation without affecting the generation of new osteoblasts. Instead, PTH increased the life-span of mature osteoblasts by preventing their apoptosis - the fate of the majority of these cells under normal conditions. The antiapoptotic effect of PTH was sufficient to account for the increase in bone mass, and was confirmed in vitro using rodent and human osteoblasts and osteocytes. This evidence provides proof of the basic principle that the work performed by a cell population can be increased by suppression of apoptosis. Moreover, it suggests novel pharmacotherapeutic strategies for osteoporosis and, perhaps, other pathologic conditions in which tissue mass diminution has compromised functional integrity.

AB - The mass of regenerating tissues, such as bone, is critically dependent on the number of executive cells, which in turn is determined by the rate of replication of progenitors and the life-span of mature cells, reflecting the timing of death by apoptosis. Bone mass can be increased by intermittent parathyroid hormone (PTH) administration, but the mechanism of this phenomenon has remained unknown. We report that daily PTH injections in mice with either normal bone mass or osteopenia due to defective osteoblastogenesis increased bone formation without affecting the generation of new osteoblasts. Instead, PTH increased the life-span of mature osteoblasts by preventing their apoptosis - the fate of the majority of these cells under normal conditions. The antiapoptotic effect of PTH was sufficient to account for the increase in bone mass, and was confirmed in vitro using rodent and human osteoblasts and osteocytes. This evidence provides proof of the basic principle that the work performed by a cell population can be increased by suppression of apoptosis. Moreover, it suggests novel pharmacotherapeutic strategies for osteoporosis and, perhaps, other pathologic conditions in which tissue mass diminution has compromised functional integrity.

UR - http://www.scopus.com/inward/record.url?scp=0032746174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032746174&partnerID=8YFLogxK

M3 - Article

C2 - 10449436

AN - SCOPUS:0032746174

VL - 104

SP - 439

EP - 446

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 4

ER -