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A mechanical Jack-like Mechanism drives spontaneous fracture healing in neonatal mice.

Abstract Treatment of fractured bones involves correction of displacement or angulation, known as reduction. However, angulated long-bone fractures in infants often heal and regain proper morphology spontaneously, without reduction. To study the mechanism underlying spontaneous regeneration of fractured bones, we left humeral fractures induced in newborn mice unstabilized, and rapid realignment of initially angulated bones was seen. This realignment was surprisingly not mediated by bone remodeling, but instead involved substantial movement of the two fragments prior to callus ossification. Analysis of gene expression profiles, cell proliferation, and bone growth revealed the formation of a functional, bidirectional growth plate at the concave side of the fracture. This growth plate acts like a mechanical jack, generating opposing forces that straighten the two fragments. Finally, we show that muscle force is important in this process, as blocking muscle contraction disrupts growth plate formation, leading to premature callus ossification and failed reduction.
PMID
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Authors

Mayor MeshTerms

Bone Regeneration

Fracture Healing

Keywords
Journal Title developmental cell
Publication Year Start




PMID- 25373776
OWN - NLM
STAT- MEDLINE
DCOM- 20150112
LR  - 20141106
IS  - 1878-1551 (Electronic)
IS  - 1534-5807 (Linking)
VI  - 31
IP  - 2
DP  - 2014 Oct 27
TI  - A mechanical Jack-like Mechanism drives spontaneous fracture healing in neonatal 
      mice.
PG  - 159-70
LID - 10.1016/j.devcel.2014.08.026 [doi]
LID - S1534-5807(14)00557-7 [pii]
AB  - Treatment of fractured bones involves correction of displacement or angulation,
      known as reduction. However, angulated long-bone fractures in infants often heal 
      and regain proper morphology spontaneously, without reduction. To study the
      mechanism underlying spontaneous regeneration of fractured bones, we left humeral
      fractures induced in newborn mice unstabilized, and rapid realignment of
      initially angulated bones was seen. This realignment was surprisingly not
      mediated by bone remodeling, but instead involved substantial movement of the two
      fragments prior to callus ossification. Analysis of gene expression profiles,
      cell proliferation, and bone growth revealed the formation of a functional,
      bidirectional growth plate at the concave side of the fracture. This growth plate
      acts like a mechanical jack, generating opposing forces that straighten the two
      fragments. Finally, we show that muscle force is important in this process, as
      blocking muscle contraction disrupts growth plate formation, leading to premature
      callus ossification and failed reduction.
FAU - Rot, Chagai
AU  - Rot C
AD  - Department of Molecular Genetics, Weizmann Institute of Science, P.O. Box 26,
      Rehovot 76100, Israel.
FAU - Stern, Tomer
AU  - Stern T
AD  - Department of Molecular Genetics, Weizmann Institute of Science, P.O. Box 26,
      Rehovot 76100, Israel.
FAU - Blecher, Ronen
AU  - Blecher R
AD  - Department of Molecular Genetics, Weizmann Institute of Science, P.O. Box 26,
      Rehovot 76100, Israel.
FAU - Friesem, Ben
AU  - Friesem B
AD  - Department of Molecular Genetics, Weizmann Institute of Science, P.O. Box 26,
      Rehovot 76100, Israel.
FAU - Zelzer, Elazar
AU  - Zelzer E
AD  - Department of Molecular Genetics, Weizmann Institute of Science, P.O. Box 26,
      Rehovot 76100, Israel. Electronic address: [email protected]
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Dev Cell
JT  - Developmental cell
JID - 101120028
SB  - IM
CIN - Dev Cell. 2014 Oct 27;31(2):137-8. PMID: 25373771
MH  - Animals
MH  - *Bone Regeneration
MH  - Bony Callus/*growth & development/metabolism
MH  - Cell Proliferation
MH  - *Fracture Healing
MH  - Fractures, Spontaneous/*therapy
MH  - Gene Expression Profiling
MH  - Growth Plate/growth & development/physiology
MH  - Mice
MH  - Muscle Contraction/physiology
MH  - Osteogenesis/*physiology
MH  - Stress, Physiological
EDAT- 2014/11/07 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/11/07 06:00
PHST- 2014/05/19 00:00 [received]
PHST- 2014/07/22 00:00 [revised]
PHST- 2014/08/28 00:00 [accepted]
PHST- 2014/11/07 06:00 [entrez]
PHST- 2014/11/07 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - S1534-5807(14)00557-7 [pii]
AID - 10.1016/j.devcel.2014.08.026 [doi]
PST - ppublish
SO  - Dev Cell. 2014 Oct 27;31(2):159-70. doi: 10.1016/j.devcel.2014.08.026.