Limits...
The interplay of osteogenesis and hematopoiesis: expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow.

Kuznetsov SA, Riminucci M, Ziran N, Tsutsui TW, Corsi A, Calvi L, Kronenberg HM, Schipani E, Robey PG, Bianco P - J. Cell Biol. (2004)

Bottom Line: The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis.This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells.Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment.

View Article: PubMed Central - PubMed

Affiliation: Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.

ABSTRACT
The ontogeny of bone marrow and its stromal compartment, which is generated from skeletal stem/progenitor cells, was investigated in vivo and ex vivo in mice expressing constitutively active parathyroid hormone/parathyroid hormone-related peptide receptor (PTH/PTHrP; caPPR) under the control of the 2.3-kb bone-specific mouse Col1A1 promoter/enhancer. The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis. This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells. Proliferative osteoprogenitors, but not multipotent skeletal stem cells (mesenchymal stem cells), capable of generating a complete heterotopic bone organ upon in vivo transplantation were assayable in the bone marrow of caPPR mice. Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment.

Show MeSH

Related in: MedlinePlus

Relative growth of marrow cavities with respect to bone over time. High resolution radiograms of tibia and fibula at 1, 3, and 5 mo. At 1 mo, a much longer primary spongiosa is observed in tg mice than in wt mice. In continuity with the extended primary spongiosa, abundant trabeculae are detected in the medullary cavity of the diaphysis. Corresponding regions in wt tibia show a bone-free marrow cavity. At 3 mo, a dense primary spongiosa is still present in the tg tibia, albeit much reduced in length compared with what is observed at 1 mo. Below this region, a marrow cavity is discernible. However, it is occupied by a dense meshwork of bone trabeculae. Corresponding regions in the wt tibia show a bone-free marrow cavity. A similar pattern is observed at 5 mo. Asterisks mark corresponding regions in the primary spongiosa, metaphysis, and diaphysis in radiograms of wt and tg mice.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2172616&req=5

fig3: Relative growth of marrow cavities with respect to bone over time. High resolution radiograms of tibia and fibula at 1, 3, and 5 mo. At 1 mo, a much longer primary spongiosa is observed in tg mice than in wt mice. In continuity with the extended primary spongiosa, abundant trabeculae are detected in the medullary cavity of the diaphysis. Corresponding regions in wt tibia show a bone-free marrow cavity. At 3 mo, a dense primary spongiosa is still present in the tg tibia, albeit much reduced in length compared with what is observed at 1 mo. Below this region, a marrow cavity is discernible. However, it is occupied by a dense meshwork of bone trabeculae. Corresponding regions in the wt tibia show a bone-free marrow cavity. A similar pattern is observed at 5 mo. Asterisks mark corresponding regions in the primary spongiosa, metaphysis, and diaphysis in radiograms of wt and tg mice.

Mentions: Radiographic analysis at multiple time points demonstrated an obvious evolution of the phenotype in tg mice over time (Fig. 3). Remodeling of the extended primary spongiosa into a secondary spongiosa was obvious at 1 mo, and continued thereafter. This process generated increasing amounts of marrow, while leaving behind a system of trabeculae, which extended well into the diaphysis of tg mice. Corresponding regions of the same wt long bones featured a fully formed marrow cavity devoid of trabecular structures. With time, a marrow cavity of near-normal length was established at 4–5 mo in tg mice.


The interplay of osteogenesis and hematopoiesis: expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow.

Kuznetsov SA, Riminucci M, Ziran N, Tsutsui TW, Corsi A, Calvi L, Kronenberg HM, Schipani E, Robey PG, Bianco P - J. Cell Biol. (2004)

Relative growth of marrow cavities with respect to bone over time. High resolution radiograms of tibia and fibula at 1, 3, and 5 mo. At 1 mo, a much longer primary spongiosa is observed in tg mice than in wt mice. In continuity with the extended primary spongiosa, abundant trabeculae are detected in the medullary cavity of the diaphysis. Corresponding regions in wt tibia show a bone-free marrow cavity. At 3 mo, a dense primary spongiosa is still present in the tg tibia, albeit much reduced in length compared with what is observed at 1 mo. Below this region, a marrow cavity is discernible. However, it is occupied by a dense meshwork of bone trabeculae. Corresponding regions in the wt tibia show a bone-free marrow cavity. A similar pattern is observed at 5 mo. Asterisks mark corresponding regions in the primary spongiosa, metaphysis, and diaphysis in radiograms of wt and tg mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172616&req=5

fig3: Relative growth of marrow cavities with respect to bone over time. High resolution radiograms of tibia and fibula at 1, 3, and 5 mo. At 1 mo, a much longer primary spongiosa is observed in tg mice than in wt mice. In continuity with the extended primary spongiosa, abundant trabeculae are detected in the medullary cavity of the diaphysis. Corresponding regions in wt tibia show a bone-free marrow cavity. At 3 mo, a dense primary spongiosa is still present in the tg tibia, albeit much reduced in length compared with what is observed at 1 mo. Below this region, a marrow cavity is discernible. However, it is occupied by a dense meshwork of bone trabeculae. Corresponding regions in the wt tibia show a bone-free marrow cavity. A similar pattern is observed at 5 mo. Asterisks mark corresponding regions in the primary spongiosa, metaphysis, and diaphysis in radiograms of wt and tg mice.
Mentions: Radiographic analysis at multiple time points demonstrated an obvious evolution of the phenotype in tg mice over time (Fig. 3). Remodeling of the extended primary spongiosa into a secondary spongiosa was obvious at 1 mo, and continued thereafter. This process generated increasing amounts of marrow, while leaving behind a system of trabeculae, which extended well into the diaphysis of tg mice. Corresponding regions of the same wt long bones featured a fully formed marrow cavity devoid of trabecular structures. With time, a marrow cavity of near-normal length was established at 4–5 mo in tg mice.

Bottom Line: The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis.This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells.Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment.

View Article: PubMed Central - PubMed

Affiliation: Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.

ABSTRACT
The ontogeny of bone marrow and its stromal compartment, which is generated from skeletal stem/progenitor cells, was investigated in vivo and ex vivo in mice expressing constitutively active parathyroid hormone/parathyroid hormone-related peptide receptor (PTH/PTHrP; caPPR) under the control of the 2.3-kb bone-specific mouse Col1A1 promoter/enhancer. The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis. This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells. Proliferative osteoprogenitors, but not multipotent skeletal stem cells (mesenchymal stem cells), capable of generating a complete heterotopic bone organ upon in vivo transplantation were assayable in the bone marrow of caPPR mice. Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment.

Show MeSH
Related in: MedlinePlus