Abstract

Lysyl oxidase (LOX) is a facilitator of extracellular matrix cross-linking. Using newly developed megakaryocyte-specific LOX knockout mice, we show that LOX expressed in these scarce bone marrow cells affects bone volume and collagen architecture in a sex-dependent manner.

1.
Kumari
S
,
Panda
TK
,
Pradhan
T
.
Lysyl oxidase: its diversity in health and diseases
.
Indian J Clin Biochem
.
2017
;
32
(
2
):
134
-
141
.
2.
Kagan
HM
,
Trackman
PC
.
Properties and function of lysyl oxidase
.
Am J Respir Cell Mol Biol
.
1991
;
5
(
3
):
206
-
210
.
3.
Eliades
A
,
Papadantonakis
N
,
Bhupatiraju
A
, et al
.
Control of megakaryocyte expansion and bone marrow fibrosis by lysyl oxidase
.
J Biol Chem
.
2011
;
286
(
31
):
27630
-
27638
.
4.
Abbonante
V
,
Chitalia
V
,
Rosti
V
, et al
.
Upregulation of lysyl oxidase and adhesion to collagen of human megakaryocytes and platelets in primary myelofibrosis
.
Blood
.
2017
;
130
(
6
):
829
-
831
.
5.
Karagianni
A
,
Ravid
K
.
Myeloproliferative disorders and their effects on bone homeostasis: the role of megakaryocytes
.
Blood
.
2022
;
139
(
21
):
3127
-
3137
.
6.
Pischon
N
,
Mäki
JM
,
Weisshaupt
P
, et al
.
Lysyl oxidase (lox) gene deficiency affects osteoblastic phenotype
.
Calcif Tissue Int
.
2009
;
85
(
2
):
119
-
126
.
7.
Daley
EJ
,
Pajevic
PD
,
Roy
S
,
Trackman
PC
.
Impaired gastric hormone regulation of osteoblasts and lysyl oxidase drives bone disease in diabetes mellitus
.
JBMR Plus
.
2019
;
3
(
10
):
e10212
-
e
.
8.
Paschalis
EP
,
Tatakis
DN
,
Robins
S
, et al
.
Lathyrism-induced alterations in collagen cross-links influence the mechanical properties of bone material without affecting the mineral
.
Bone
.
2011
;
49
(
6
):
1232
-
1241
.
9.
McNerny
EM
,
Gong
B
,
Morris
MD
,
Kohn
DH
.
Bone fracture toughness and strength correlate with collagen cross-link maturity in a dose-controlled lathyrism mouse model
.
J Bone Miner Res
.
2015
;
30
(
3
):
455
-
464
.
10.
Ida
T
,
Kaku
M
,
Kitami
M
, et al
.
Extracellular matrix with defective collagen cross-linking affects the differentiation of bone cells
.
PLoS One
.
2018
;
13
(
9
):
e0204306
.
11.
Hong
HH
,
Pischon
N
,
Santana
RB
, et al
.
A role for lysyl oxidase regulation in the control of normal collagen deposition in differentiating osteoblast cultures
.
J Cell Physiol
.
2004
;
200
(
1
):
53
-
62
.
12.
Turecek
C
,
Fratzl-Zelman
N
,
Rumpler
M
, et al
.
Collagen cross-linking influences osteoblastic differentiation
.
Calcif Tissue Int
.
2008
;
82
(
5
):
392
-
400
.
13.
Khosravi
R
,
Sodek
KL
,
Xu
WP
, et al
.
A novel function for lysyl oxidase in pluripotent mesenchymal cell proliferation and relevance to inflammation-associated osteopenia
.
PLoS One
.
2014
;
9
(
6
):
e100669
.
14.
Sharma-Bhandari
A
,
Park
SH
,
Kim
JY
,
Oh
J
,
Kim
Y
.
Lysyl oxidase modulates the osteoblast differentiation of primary mouse calvaria cells
.
Int J Mol Med
.
2015
;
36
(
6
):
1664
-
1670
.
15.
Stavnichuk
M
,
Komarova
SV
.
Megakaryocyte-bone cell interactions: lessons from mouse models of experimental myelofibrosis and related disorders
.
Am J Physiol Cell Physiol
.
2022
;
322
(
2
):
C177
-
C184
.
16.
Karagianni
A
,
Matsuura
S
,
Gerstenfeld
LC
,
Ravid
K
.
Inhibition of osteoblast differentiation by JAK2V617F megakaryocytes derived from male mice with primary myelofibrosis
.
Front Oncol
.
2022
;
12
:
929498
.
17.
Gaytan
F
,
Morales
C
,
Reymundo
C
,
Tena-Sempere
M
.
A novel RGB-trichrome staining method for routine histological analysis of musculoskeletal tissues
.
Sci Rep
.
2020
;
10
(
1
):
16659
.
18.
Leiva
O
,
Ng
SK
,
Matsuura
S
, et al
.
Novel lysyl oxidase inhibitors attenuate hallmarks of primary myelofibrosis in mice
.
Int J Hematol
.
2019
;
110
(
6
):
699
-
708
.
19.
Page-McCaw
A
,
Ewald
AJ
,
Werb
Z
.
Matrix metalloproteinases and the regulation of tissue remodelling
.
Nat Rev Mol Cell Biol
.
2007
;
8
(
3
):
221
-
233
.
20.
Ricard-Blum
S
.
The collagen family
.
Cold Spring Harb Perspect Biol
.
2011
;
3
(
1
):
a004978
.
21.
Lu
D
,
Demissie
S
,
Horowitz
NB
, et al
.
Temporal and quantitative transcriptomic differences define sexual dimorphism in murine postnatal bone aging
.
JBMR Plus
.
2022
;
6
(
2
):
e10579
.
22.
Xu
Q
,
Streuer
A
,
Jann
JC
, et al
.
Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies
.
Nat Commun
.
2023
;
14
(
1
):
1497
.
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