Evidence for articular cartilage regeneration in MRLMpJ mice

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Evidence for articular cartilage regeneration in
MRL/MpJ mice

• J. Fitzgerald Ph.D.yz, C. Rich M.S.y, D.
  Burkhardt B.S.x, J. Allen Ph.D.z, A. S. Herzka
  M.D.
• and C. B. Little B.V.M.S., Phd
• Oregon Health and Science University, Portland,
  OR,USA
• University of Melbourne, Murdoch Childrens
  Research Institute, Royal Childrens Hospital,
  Melbourne, Australia
• Raymond Purves Bone and Joint Research
  Laboratories, Kolling Institute of Medical
  Research, University of Sydney, Royal North
  Shore Hospital, Sydney, Australia

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Osteoarthritis

• Causes
• Primary
• Secondary
• Genetic Basis
• Incidence
• Male
• Female
• Newer Techniques
• MRL/MpJ strain Vs C57BI/6
• Epimorphic Regeneration In MRL/MpJ

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• In consistent with the tissue regeneration in
  MRL/MpJ strain, the MRL/MpJ strain does
  indeed possess a capacity to regenerate or
  repair articular cartilage following full
  thickness lesion.

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Materials and Methods

• Age, 8 weeks
• Anaesthesia
• Full Thickness lesions
• with 27G needle
• Partial thickness lesion
• with opthalmic scalpel

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Anatomical location of full thickness lesion
(circle) and partial thickness laceration (line)
in the trochlear groove. The joint capsule of the
right hindlimb was opened and the patella
subluxated to the left to expose the trochlear
groove. The full thickness defect was made on the
proximal part of the trochlear and the partial
thickness lesion distal to this.
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Analysis of articular cartilage lesions at 6
weeks timepoint. Representative sagittal
sections of full thickness lesions from four
C57Bl/6 (left) and MRL/MpJ (right) mice stained
with toluidine blue for proteoglycan. The MRL
mice have significant proteoglycan deposition
comparedto the C57Bl/6 control strain.
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HISTOLOGICAL SCORE FOR FULL THICKNESS CARTILAGE
LESIONS

• Histological Score at 6 weeks

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Partial Thickness Lesions Scoring
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Representative sagittal sections of full
thickness lesions from three C57Bl/6 (left) and
MRL/MpJ (right) mice stained with toluidine blue.
The MRL mice have extensive proteoglycan
deposition compared with the C57Bl/6 control
strain, which in the majority of mice have no
metachromatic staining.
Analysis of full thickness cartilage lesions 12
weeks following surgery.
Representative sagittal sections of full
thickness from MRL/MpJ (panels b, e, i) and
C57Bl/6 mice (panels c, f, j). Non-operated
C57Bl/6 mice (panels a, d, h) and sections
stained with secondary antibody only serve as
controls (panels g, k). Sections were stained for
the presence of proteoglycans (toluidine blue),
collagenII and collagen VI. The MRL/MpJ mice have
extensive proteoglycan, collagen II and collagen
VI deposition in the lesion compared with the
C57/Bl6 control strain. Panels aeg, k are 10 and
panels h, i, j are 20. Panel l is a higher power
image (40) of proteoglycanstained MRL/MpJ lesion.
Note the abundance of chondrocyte-like cells in
the lesion.
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Full Thickness Lesions at 12 weeks
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Representative sagittal section of partial
thickness cartilage lesions at 12 weeks after
surgery stained with toluidine blue
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Analysis of ear hole closure in MRL/MpJ and
C57bl/6 mice 12 weeks post-surgery.
Representative examples of ear hole closure from
three C57Bl/6 (above) and MRL/MpJ (below) mice.
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Mean Standard Deviation of ear hole closure
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Conclusions

• Cartilage Regeneration in MRL/MpJ strain
• Sexual Dimorphism Male gt female _at_ 12 wks
• Female gt
  male _at_ 6wks
• Time Frames
• Genetic aspect Ear hole and Cartilage
  regeneration
• Full Vs partial Thickness lesions healing
• Ear hole lesion affecting cartilage Healing

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Little more.
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Absence of Posttraumatic Arthritis
FollowingIntraarticular Fracture in the MRL/MpJ
Mouse

• Benjamin D. Ward, Bridgette D. Furman, Janet L.
  Huebner, Virginia B. Kraus,
• Farshid Guilak, and Steven A. Olson

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Knee and Tibial Plateau
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Histologic evaluation of articular cartilage. A,
Lateral compartment of the contralateral control
joint and the experimental(fractured) joint (in
the coronal plane) from the same C57BL/6 mouse
shown in Figure 1, demonstrating cartilage
disruption and degeneration,fibrocartilage, and
loss of proteoglycan staining (red). B, Lateral
compartment of the contralateral control joint
and the fractured joint(in the coronal plane)
from the same MRL/MpJ mouse shown in Figure 1,
demonstrating articular cartilage disruption with
no fibrocartilage and minimal loss of staining.
Boxed areas show sites of histologic damage.
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Classification of intraarticular tibial plateau
fractures. Microfocal computed tomography scans
of the contralateral control limb and the
experimental (fractured) limb in A, a C57BL/6
mouse and B, an MRL/MpJ mouse show similar
intraarticular fractures in the experimental limb
in each mouse strain, with disruption of
subchondral and periarticular bone in the lateral
region of the tibial plateau after fracture
(arrows).
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Padma Pradeepa SrinivasanCurrent Visiting
scholarProspective Masters student.
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