Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading

S. Imai, T. J. Heino, A. Hienola, Kosaku Kurata, K. Büki, Y. Matsusue, H. K. Väänänen, H. Rauvala

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

HB-GAM (also known as pleiotrophin) is a cell matrix-associated protein that is highly expressed in bone. It affects osteoblast function, and might therefore play a role in bone development and remodeling. We aimed to investigate the role of HB-GAM in bone in vivo and in vitro. The bones of HB-GAM deficient mice with an inbred mouse background were studied by histological, histomorphometrical, radiological, biomechanical and μ-CT analyses and the effect of immobilization was evaluated. HB-GAM localization in vivo was studied. MLO-Y4 osteocytes were subjected to fluid shear stress in vitro, and gene and protein expression were studied by subtractive hybridization, quantitative PCR and Western blot. Human osteoclasts were cultured in the presence of rhHB-GAM and their formation and resorption activities were assayed. In agreement with previous reports, the skeletal structure of the HB-GAM knockout mice developed normally. However, a growth retardation of the weight-bearing bones was observed by 2 months of age, suggesting a link to physical activity. Adult HB-GAM deficient mice were characterized by low bone formation and osteopenia, as well as resistance to immobilization-dependent bone remodeling. HB-GAM was localized around osteocytes and their processes in vivo and furthermore, osteocytic HB-GAM expression was upregulated by mechanical loading in vitro. HB-GAM did not affect on human osteoclast formation or resorption in vitro. Taken together, our results suggest that HB-GAM is an osteocyte-derived factor that could participate in mediating the osteogenic effects of mechanical loading on bone.

Original languageEnglish
Pages (from-to)785-794
Number of pages10
JournalBone
Volume44
Issue number5
DOIs
Publication statusPublished - May 1 2009

Fingerprint

Osteocytes
Osteogenesis
Bone and Bones
Bone Remodeling
Osteoclasts
Immobilization
pleiotrophin
Metabolic Bone Diseases
Bone Development
Weight-Bearing
Osteoblasts
Knockout Mice
Proteins
Western Blotting

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Imai, S., Heino, T. J., Hienola, A., Kurata, K., Büki, K., Matsusue, Y., ... Rauvala, H. (2009). Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading. Bone, 44(5), 785-794. https://doi.org/10.1016/j.bone.2009.01.004

Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading. / Imai, S.; Heino, T. J.; Hienola, A.; Kurata, Kosaku; Büki, K.; Matsusue, Y.; Väänänen, H. K.; Rauvala, H.

In: Bone, Vol. 44, No. 5, 01.05.2009, p. 785-794.

Research output: Contribution to journalArticle

Imai, S, Heino, TJ, Hienola, A, Kurata, K, Büki, K, Matsusue, Y, Väänänen, HK & Rauvala, H 2009, 'Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading', Bone, vol. 44, no. 5, pp. 785-794. https://doi.org/10.1016/j.bone.2009.01.004
Imai, S. ; Heino, T. J. ; Hienola, A. ; Kurata, Kosaku ; Büki, K. ; Matsusue, Y. ; Väänänen, H. K. ; Rauvala, H. / Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading. In: Bone. 2009 ; Vol. 44, No. 5. pp. 785-794.
@article{0dd2998bd9a94a18b15ab01e2848e588,
title = "Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading",
abstract = "HB-GAM (also known as pleiotrophin) is a cell matrix-associated protein that is highly expressed in bone. It affects osteoblast function, and might therefore play a role in bone development and remodeling. We aimed to investigate the role of HB-GAM in bone in vivo and in vitro. The bones of HB-GAM deficient mice with an inbred mouse background were studied by histological, histomorphometrical, radiological, biomechanical and μ-CT analyses and the effect of immobilization was evaluated. HB-GAM localization in vivo was studied. MLO-Y4 osteocytes were subjected to fluid shear stress in vitro, and gene and protein expression were studied by subtractive hybridization, quantitative PCR and Western blot. Human osteoclasts were cultured in the presence of rhHB-GAM and their formation and resorption activities were assayed. In agreement with previous reports, the skeletal structure of the HB-GAM knockout mice developed normally. However, a growth retardation of the weight-bearing bones was observed by 2 months of age, suggesting a link to physical activity. Adult HB-GAM deficient mice were characterized by low bone formation and osteopenia, as well as resistance to immobilization-dependent bone remodeling. HB-GAM was localized around osteocytes and their processes in vivo and furthermore, osteocytic HB-GAM expression was upregulated by mechanical loading in vitro. HB-GAM did not affect on human osteoclast formation or resorption in vitro. Taken together, our results suggest that HB-GAM is an osteocyte-derived factor that could participate in mediating the osteogenic effects of mechanical loading on bone.",
author = "S. Imai and Heino, {T. J.} and A. Hienola and Kosaku Kurata and K. B{\"u}ki and Y. Matsusue and V{\"a}{\"a}n{\"a}nen, {H. K.} and H. Rauvala",
year = "2009",
month = "5",
day = "1",
doi = "10.1016/j.bone.2009.01.004",
language = "English",
volume = "44",
pages = "785--794",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading

AU - Imai, S.

AU - Heino, T. J.

AU - Hienola, A.

AU - Kurata, Kosaku

AU - Büki, K.

AU - Matsusue, Y.

AU - Väänänen, H. K.

AU - Rauvala, H.

PY - 2009/5/1

Y1 - 2009/5/1

N2 - HB-GAM (also known as pleiotrophin) is a cell matrix-associated protein that is highly expressed in bone. It affects osteoblast function, and might therefore play a role in bone development and remodeling. We aimed to investigate the role of HB-GAM in bone in vivo and in vitro. The bones of HB-GAM deficient mice with an inbred mouse background were studied by histological, histomorphometrical, radiological, biomechanical and μ-CT analyses and the effect of immobilization was evaluated. HB-GAM localization in vivo was studied. MLO-Y4 osteocytes were subjected to fluid shear stress in vitro, and gene and protein expression were studied by subtractive hybridization, quantitative PCR and Western blot. Human osteoclasts were cultured in the presence of rhHB-GAM and their formation and resorption activities were assayed. In agreement with previous reports, the skeletal structure of the HB-GAM knockout mice developed normally. However, a growth retardation of the weight-bearing bones was observed by 2 months of age, suggesting a link to physical activity. Adult HB-GAM deficient mice were characterized by low bone formation and osteopenia, as well as resistance to immobilization-dependent bone remodeling. HB-GAM was localized around osteocytes and their processes in vivo and furthermore, osteocytic HB-GAM expression was upregulated by mechanical loading in vitro. HB-GAM did not affect on human osteoclast formation or resorption in vitro. Taken together, our results suggest that HB-GAM is an osteocyte-derived factor that could participate in mediating the osteogenic effects of mechanical loading on bone.

AB - HB-GAM (also known as pleiotrophin) is a cell matrix-associated protein that is highly expressed in bone. It affects osteoblast function, and might therefore play a role in bone development and remodeling. We aimed to investigate the role of HB-GAM in bone in vivo and in vitro. The bones of HB-GAM deficient mice with an inbred mouse background were studied by histological, histomorphometrical, radiological, biomechanical and μ-CT analyses and the effect of immobilization was evaluated. HB-GAM localization in vivo was studied. MLO-Y4 osteocytes were subjected to fluid shear stress in vitro, and gene and protein expression were studied by subtractive hybridization, quantitative PCR and Western blot. Human osteoclasts were cultured in the presence of rhHB-GAM and their formation and resorption activities were assayed. In agreement with previous reports, the skeletal structure of the HB-GAM knockout mice developed normally. However, a growth retardation of the weight-bearing bones was observed by 2 months of age, suggesting a link to physical activity. Adult HB-GAM deficient mice were characterized by low bone formation and osteopenia, as well as resistance to immobilization-dependent bone remodeling. HB-GAM was localized around osteocytes and their processes in vivo and furthermore, osteocytic HB-GAM expression was upregulated by mechanical loading in vitro. HB-GAM did not affect on human osteoclast formation or resorption in vitro. Taken together, our results suggest that HB-GAM is an osteocyte-derived factor that could participate in mediating the osteogenic effects of mechanical loading on bone.

UR - http://www.scopus.com/inward/record.url?scp=63449105137&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63449105137&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2009.01.004

DO - 10.1016/j.bone.2009.01.004

M3 - Article

C2 - 19442624

AN - SCOPUS:63449105137

VL - 44

SP - 785

EP - 794

JO - Bone

JF - Bone

SN - 8756-3282

IS - 5

ER -