Publications by authors named "Hui Jean Kok"

3 Publications

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Actions and interactions of IGF-I and MMPs during muscle regeneration.

Semin Cell Dev Biol 2021 May 4. Epub 2021 May 4.

Applied Physiology & Kinesiology, College of Health and Human Performance, University of Florida, 1864 Stadium Road, Gainesville, FL 32611, USA. Electronic address:

Muscle regeneration requires the coordination of several factors to mobilize satellite cells and macrophages, remodel the extracellular matrix surrounding muscle fibers, and repair existing and/or form new muscle fibers. In this review, we focus on insulin-like growth factor I and the matrix metalloproteinases, which are secreted proteins that act on cells and the matrix to resolve damage. While their actions appear independent, their interactions occur at the transcriptional and post-translational levels to promote feed-forward activation of each other. Together, these proteins assist at virtually every step of the repair process, and contribute significantly to muscle regenerative capacity.
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http://dx.doi.org/10.1016/j.semcdb.2021.04.018DOI Listing
May 2021

Matrix Metalloproteinase 13 from Satellite Cells is Required for Efficient Muscle Growth and Regeneration.

Cell Physiol Biochem 2020 Apr;54(3):333-353

Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA,

Background/aims: Cell migration and extracellular matrix remodeling underlie normal mammalian development and growth as well as pathologic tumor invasion. Skeletal muscle is no exception, where satellite cell migration replenishes nuclear content in damaged tissue and extracellular matrix reforms during regeneration. A key set of enzymes that regulate these processes are matrix metalloproteinases (MMP)s. The collagenase MMP-13 is transiently upregulated during muscle regeneration, but its contribution to damage resolution is unknown. The purpose of this work was to examine the importance of MMP-13 in muscle regeneration and growth in vivo and to delineate a satellite cell specific role for this collagenase.

Methods: Mice with total and satellite cell specific Mmp13 deletion were utilized to determine the importance of MMP-13 for postnatal growth, regeneration after acute injury, and in chronic injury from a genetic cross with dystrophic (mdx) mice. We also evaluated insulin-like growth factor 1 (IGF-1) mediated hypertrophy in the presence and absence of MMP-13. We employed live-cell imaging and 3D migration measurements on primary myoblasts obtained from these animals. Outcome measures included muscle morphology and function.

Results: Under basal conditions, Mmp13 mice did not exhibit histological or functional deficits in muscle. However, following acute injury, regeneration was impaired at 11 and 14 days post injury. Muscle hypertrophy caused by increased IGF-1 was blunted with minimal satellite cell incorporation in the absence of MMP-13. Mmp13 primary myoblasts displayed reduced migratory capacity in 2D and 3D, while maintaining normal proliferation and differentiation. Satellite cell specific deletion of MMP-13 recapitulated the effects of global MMP-13 ablation on muscle regeneration, growth and myoblast movement.

Conclusion: These results show that satellite cells provide an essential autocrine source of MMP-13, which not only regulates their migration, but also supports postnatal growth and resolution of acute damage.
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http://dx.doi.org/10.33594/000000223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293591PMC
April 2020

Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury.

J Neurosci Res 2020 05 4;98(5):843-868. Epub 2019 Dec 4.

Research Service, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, USA.

Loading and testosterone may influence musculoskeletal recovery after spinal cord injury (SCI). Our objectives were to determine (a) the acute effects of bodyweight-supported treadmill training (TM) on hindlimb cancellous bone microstructure and muscle mass in adult rats after severe contusion SCI and (b) whether longer-term TM with adjuvant testosterone enanthate (TE) delivers musculoskeletal benefit. In Study 1, TM (40 min/day, 5 days/week, beginning 1 week postsurgery) did not prevent SCI-induced hindlimb cancellous bone loss after 3 weeks. In Study 2, TM did not attenuate SCI-induced plantar flexor muscles atrophy nor improve locomotor recovery after 4 weeks. In our main study, SCI produced extensive distal femur and proximal tibia cancellous bone deficits, a deleterious slow-to-fast fiber-type transition in soleus, lower muscle fiber cross-sectional area (fCSA), impaired muscle force production, and levator ani/bulbocavernosus (LABC) muscle atrophy after 8 weeks. TE alone (7.0 mg/week) suppressed bone resorption, attenuated cancellous bone loss, constrained the soleus fiber-type transition, and prevented LABC atrophy. In comparison, TE+TM concomitantly suppressed bone resorption and stimulated bone formation after SCI, produced near-complete cancellous bone preservation, prevented the soleus fiber-type transition, attenuated soleus fCSA atrophy, maintained soleus force production, and increased LABC mass. 75% of SCI+TE+TM animals recovered voluntary over-ground hindlimb stepping, while no SCI and only 20% of SCI+TE animals regained stepping ability. Positive associations between testosterone and locomotor function suggest that TE influenced locomotor recovery. In conclusion, short-term TM alone did not improve bone, muscle, or locomotor recovery in adult rats after severe SCI, while longer-term TE+TM provided more comprehensive musculoskeletal benefit than TE alone.
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http://dx.doi.org/10.1002/jnr.24564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072003PMC
May 2020