PMID- 33212319
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20220531
IS  - 1873-2763 (Electronic)
IS  - 8756-3282 (Print)
IS  - 1873-2763 (Linking)
VI  - 143
DP  - 2021 Feb
TI  - Osteoblastic monocyte chemoattractant protein-1 (MCP-1) mediation of parathyroid 
      hormone's anabolic actions in bone implicates TGF-beta signaling.
PG  - 115762
LID - S8756-3282(20)30550-0 [pii]
LID - 10.1016/j.bone.2020.115762 [doi]
AB  - Parathyroid hormone (PTH) is necessary for the regulation of calcium homeostasis 
      and PTH (1-34) was the first approved osteoanabolic therapy for osteoporosis. It 
      is well established that intermittent PTH increases bone formation and that bone 
      remodeling and several cytokines and chemokines play an essential role in this 
      process. Earlier, we had established that the chemokine, monocyte chemoattractant 
      protein-1 (MCP-1/CCL2), was the most highly stimulated gene in rat bone after 
      intermittent PTH injections. Nevertheless, MCP-1 function in bone appears to be 
      complicated. To identify the primary cells expressing MCP-1 in response to PTH, 
      we performed in situ hybridization of rat bone sections after hPTH (1-34) 
      injections and showed that bone-lining osteoblasts are the primary cells that 
      express MCP-1 after PTH treatment. We previously demonstrated MCP-1's importance 
      by showing that PTH's anabolic effects are abolished in MCP-1 null mice, further 
      implicating a role for the chemokine in this process. To establish whether 
      rhMCP-1 peptide treatment could rescue the anabolic effect of PTH in MCP-1 null 
      mice, we treated 4-month-old wild-type (WT) mice with hPTH (1-34) and MCP-1(-/-) 
      mice with rhMCP-1 and/or hPTH (1-34) for 6 weeks. Micro-computed tomography (muCT) 
      analysis of trabecular and cortical bone showed that MCP-1 injections for 6 weeks 
      rescued the PTH anabolic effect in MCP-1(-/-) mice. In fact, the combination of 
      rhMCP-1 and hPTH (1-34) has a synergistic anabolic effect compared with 
      monotherapies. Mechanistically, PTH-enhanced transforming growth factor-beta (TGF-beta) 
      signaling is abolished in the absence of MCP-1, while MCP-1 peptide treatment 
      restores TGF-beta signaling in the bone marrow. Here, we have shown that PTH 
      regulates the transcription of the chemokine MCP-1 in osteoblasts and determined 
      how MCP-1 affects bone cell function in PTH's anabolic actions. Taken together, 
      our current work indicates that intermittent PTH stimulates osteoblastic 
      secretion of MCP-1, which leads to increased TGF-beta signaling, implicating it in 
      PTH's anabolic actions.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Siddiqui, Jawed A
AU  - Siddiqui JA
AD  - Department of Molecular Pathobiology, New York University College of Dentistry, 
      New York, United States of America.
FAU - Le Henaff, Carole
AU  - Le Henaff C
AD  - Department of Molecular Pathobiology, New York University College of Dentistry, 
      New York, United States of America.
FAU - Johnson, Joshua
AU  - Johnson J
AD  - Department of Molecular Pathobiology, New York University College of Dentistry, 
      New York, United States of America.
FAU - He, Zhiming
AU  - He Z
AD  - Department of Molecular Pathobiology, New York University College of Dentistry, 
      New York, United States of America.
FAU - Rifkin, Daniel B
AU  - Rifkin DB
AD  - Department of Cell Biology, New York University Grossman School of Medicine, New 
      York, United States of America.
FAU - Partridge, Nicola C
AU  - Partridge NC
AD  - Department of Molecular Pathobiology, New York University College of Dentistry, 
      New York, United States of America. Electronic address: ncp234@nyu.edu.
LA  - eng
GR  - S10 OD010751/OD/NIH HHS/United States
GR  - UL1 TR001445/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20201117
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (Anabolic Agents)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - *Anabolic Agents/pharmacology
MH  - Animals
MH  - Bone and Bones
MH  - Chemokine CCL2
MH  - Mice
MH  - Osteoblasts
MH  - Parathyroid Hormone/pharmacology
MH  - Rats
MH  - *Transforming Growth Factor beta
MH  - X-Ray Microtomography
PMC - PMC8628523
MID - NIHMS1653990
OTO - NOTNLM
OT  - Bone
OT  - Chemokines
OT  - Monocyte chemoattractant protein-1
OT  - Osteoporosis
OT  - PTH
EDAT- 2020/11/20 06:00
MHDA- 2021/06/22 06:00
PMCR- 2022/02/01
CRDT- 2020/11/19 20:10
PHST- 2020/06/19 00:00 [received]
PHST- 2020/11/12 00:00 [revised]
PHST- 2020/11/14 00:00 [accepted]
PHST- 2020/11/20 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/11/19 20:10 [entrez]
PHST- 2022/02/01 00:00 [pmc-release]
AID - S8756-3282(20)30550-0 [pii]
AID - 10.1016/j.bone.2020.115762 [doi]
PST - ppublish
SO  - Bone. 2021 Feb;143:115762. doi: 10.1016/j.bone.2020.115762. Epub 2020 Nov 17.