Publications

RECENT PUBLICATIONS

Liu X, Liu M, Lee L, Davies M, Wang Z, Kim H, Feeley BT. Trichostatin A Regulates Fibro/adipogenic Progenitor Adipogenesis Epigenetically and Reduces

Rotator Cuff Muscle Fatty Infiltration. J Orthop Res. 2020 Sep 24. doi:10.1002/jor.24865. Epub ahead of print. PMID: 32970360.

This study demonstrated that treatment of injured rotator cuff muscle with a histone deacetylase inhibitor, Trichostatin A, decreases fibroadipogenic progenitor-mediated fatty infiltration and muscle atrophy. 

Feeley BT, Liu M, Ma CB, Agha O, Aung M, Lee C, Liu X. Human Rotator Cuff Tears Have an Endogenous, Inducible Stem Cell Source Capable of Improving Muscle

Quality and Function After Rotator Cuff Repair. Am J Sports Med. 2020 Sep;48(11):2660-2668. doi: 10.1177/0363546520935855. Epub 2020 Jul 30. PMID:

32730704.

This study is the first study that shows the FAP cell population in human rotator cuff tears.  We found that patients with rotator cuff tears had more FAPs if they were older, and if the tears were larger.  The FAP stem cells were inducible to a pro-myogenic beige fat phenotype.  This study proved that these stem cells are the likely cellular source of fatty infiltration and likely promote muscle atrophy.

 

Agha O, Diaz A, Davies M, Kim HT, Liu X, Feeley BT. Rotator cuff tear degeneration and the role of fibro-adipogenic progenitors. Ann N Y Acad Sci.

2020 Jul 29. doi: 10.1111/nyas.14437. Epub ahead of print. PMID: 32725671.

 

Agha O, Mueller-Immergluck A, Liu M, Zhang H, Theologis AA, Clark A, Kim HT, Liu X, Feeley BT, Bailey JF. Intervertebral disc herniation effects on

multifidus muscle composition and resident stem cell populations. JOR Spine. 2020 May 6;3(2):e1091. doi: 10.1002/jsp2.1091. PMID: 32613166; PMCID:

PMC7323461.

In a collaborative effort with the UCSF spine surgery team, we found that low back pain patients have increased FAP cells, which likely contributes to the muscle degeneration seen in the large paraspinal muscles.

 

Lee C, Liu M, Agha O, Kim HT, Liu X, Feeley BT. Beige fibro-adipogenic progenitor transplantation reduces muscle degeneration and improves function in a mouse model of delayed repair of rotator cuff tears. J Shoulder Elbow Surg. 2019 Nov 26. pii: S1058-2746(19)30648-2. doi: 10.1016/j.jse.2019.09.021. 
PMID: 31784382
We performed FAP stem cell transplantation to improve outcomes after rotator cuff injury in a mouse model of rotator cuff repair. Cell transplantation diminished fibrosis, FI, and atrophy and enhanced vascularization in both delayed repair models. Cell transplantation resulted in improved shoulder function as assessed with gait analysis in both the delayed repair models.

Wang Z, Liu X, Davies MR, Horne D, Kim H, Feeley BT.
A Mouse Model of Delayed Rotator Cuff Repair Results in Persistent Muscle Atrophy and Fatty Infiltration. Am J Sports Med. 2018 Oct;46(12):2981-2989. doi: 10.1177/0363546518793403. Epub 2018 Sep 10.
This study evaluated a novel mouse model that we developed to study rotator cuff repairs. We found that a mouse model was able to reproduce a phenomenon we have seen in clinical populations: that even in the setting of a successful repair, there is persistent atrophy and fatty infiltration. We also used gait analysis (picture a teeny tiny treadmill) to show that shoulder function was not as good as if there had been no injury or repair. We are currently using this model to evaluate treatment strategies to improve rotator cuff function by stimulating stem cell development.  

Wang Z, Feeley BT, Kim HT, Liu X.
Reversal of Fatty Infiltration After Suprascapular Nerve Compression Release Is Dependent on UCP1 Expression in Mice.
Clin Orthop Relat Res. 2018 Aug;476(8):1665-1679. doi: 10.1097/CORR.0000000000000335.
This study looked at the influence of nerve injury in the development of fatty infiltration and muscle atrophy.  We were able to develop a reversible nerve injury and show that re-innervation results in improved muscle quality through increased FAP/beige fat expression.

Liu X, Ravishankar B, Ning A, Liu M, Kim HT, Feeley BT. Knocking-out matrix metalloproteinase-13 exacerbates rotator cuff muscle fatty infiltration. Muscles
Ligaments Tendons J.
2017 Sep 18;7(2):202-207. doi: 10.11138/mltj/2017.7.2.202. eCollection 2017 Apr-Jun. PubMed PMID: 29264329; PubMed Central PMCID:
PMC5725167.
Matrix metalloproteinase-13 plays a crucial role in extracellular matrix remodeling in many physiological and pathological processes. Nevertheless, its role in rotator cuff muscle atrophy and fatty infiltration remains unknown. Six weeks after RC surgery, no significant difference in muscle atrophy and fibrosis between MMP-13 knockout and wild type mice was observed. However, there was a significant increase in the amount of fatty infiltration in MMP-13 knockout mice compared to the wild types. Results from this study suggest that MMP-13 plays a crucial role in rotator cuff muscle fatty degeneration. This novel finding suggests a new molecular mechanism that governs RC muscle FI and MMP-13 may serve as a target for therapeutics to treat muscle FI after RC tears.
 
Davies MR, Garcia S, Tamaki S, Liu X, Lee S, Jose A, Pomerantz JH, Feeley BT. Muscle Stem Cell Activation in a Mouse Model of Rotator Cuff Injury. J Orthop
Res.
2017 Aug 8. doi: 10.1002/jor.23679. [Epub ahead of print] PubMed PMID: 28786534; PubMed Central PMCID: PMC5803476.
In this study, we characterized the longitudinal effect of rotator cuff (RC) tendon injury on the muscle stem cell (MuSC) population in mice, using a mouse model of rotator cuff tear. We found that MuSCs are transiently activated following injury before returning to their baseline state, and are not depleted, in spite of persistent muscle atrophy. Thus, factors beyond the MuSC population may be primarily responsible for the atrophy seen after RC tears, however, retained MuSCs in injured RC muscle represent a source of cells which may be induced to participate in repair to improve clinical outcomes.
 
Davies MR, Lee L, Feeley BT, Kim HT, Liu X. Lysophosphatidic acid-induced RhoA signaling and prolonged macrophage infiltration worsens fibrosis and fatty
infiltration following rotator cuff tears. J Orthop Res. 2017 Jul;35(7):1539-1547. doi: 10.1002/jor.23384. Epub 2016 Aug 19. PubMed PMID:
27505847; PubMed Central PMCID: PMC5502767.
We used the RhoA activator lysophosphatidic acid (LPA) to potentiate an inflammatory state within injured rotator cuff muscle in a mouse model of rotator cuff (RC) tear. We found that increasing RhoA signaling using LPA increased the number of CD68+ macrophages in injured muscle, which correlated with worsened rotator cuff atrophy, fibrosis, and fatty infiltration. Together, our results suggest that macrophage-mediated inflammation may play an important role in the pathogenesis of muscle degeneration following RC tear, and may represent a target for new treatments to improve muscle quality following this injury.

Davies MR, Lee L, Feeley BT, Kim HT, Liu X. Lysophosphatidic acid-induced RhoA signaling and prolonged macrophage infiltration worsens fibrosis and fatty infiltration following rotator cuff tears. J Orthop Res. 2016 Aug 9. doi: 10.1002/jor.23384. PubMed PMID: 27505847.

Liu X, Ning AY, Chang NC, Kim H, Nissenson R, Wang L, Feeley BT. Investigating the cellular origin of rotator cuff muscle fatty infiltration and fibrosis after  injury. Muscles Ligaments Tendons J. 2016 May 19;6(1):6-15. doi: 10.11138/mltj/2016.6.1.006. PubMed PMID: 27331027; PubMed Central PMCID: PMC4915463.

Davies MR, Liu X, Lee L, Laron D, Ning AY, Kim HT, Feeley BT. TGF-β Small Molecule Inhibitor SB431542 Reduces Rotator Cuff Muscle Fibrosis and Fatty Infiltration By Promoting Fibro/Adipogenic Progenitor Apoptosis. PLoS One. 2016 May 17;11(5):e0155486. doi: 10.1371/journal.pone.0155486. PubMed PMID: 27186977; PubMed Central PMCID: PMC4871364.

Liu M, Lee C, Laron D, Zhang N, Waldorff EI, Ryaby JT, Feeley B, Liu X. Role of pulsed electromagnetic fields (PEMF) on tenocytes and myoblasts-Potential application for treating rotator cuff tears. J Orthop Res. 2016 May 2. doi: 10.1002/jor.23278. [Epub ahead of print] PubMed PMID: 27138553.

Liu X, Joshi S, Ravishankar B, Laron D, Kim HT, Feeley BT. Bone morphogenetic  protein signaling in rotator cuff muscle atrophy and fatty infiltration. Muscles Ligaments Tendons J. 2015 Jul 3;5(2):113-9. PubMed PMID: 26261790; PubMed Central PMCID: PMC4496010.

Luan T, Liu X, Easley JT, Ravishankar B, Puttlitz C, Feeley BT. Muscle atrophy and fatty infiltration after an acute rotator cuff repair in a sheep model. Muscles Ligaments Tendons J. 2015 Jul 3;5(2):106-12. PubMed PMID: 26261789; PubMed Central PMCID: PMC4496009.

Davies MR, Ravishankar B, Laron D, Kim HT, Liu X, Feeley BT. Rat rotator cuff muscle responds differently from hindlimb muscle to a combined tendon-nerve injury. J Orthop Res. 2015 Jul;33(7):1046-53. doi: 10.1002/jor.22864. PubMed PMID: 25974842.

Liu X, Joshi SK, Ravishankar B, Laron D, Kim HT, Feeley BT. Upregulation of transforming growth factor-β signaling in a rat model of rotator cuff tears. J Shoulder Elbow Surg. 2014 Nov;23(11):1709-16. doi: 10.1016/j.jse.2014.02.029. PubMed PMID: 24875732; PubMed Central PMCID: PMC4198422.

Joshi SK, Kim HT, Feeley BT, Liu X. Differential ubiquitin-proteasome and autophagy signaling following rotator cuff tears and suprascapular nerve injury. J Orthop Res. 2014 Jan;32(1):138-44. doi: 10.1002/jor.22482. PubMed PMID: 24018537; PubMed Central PMCID: PMC3856942.

Kramer EJ, Bodendorfer BM, Laron D, Wong J, Kim HT, Liu X, Feeley BT. Evaluation of cartilage degeneration in a rat model of rotator cuff tear arthropathy. J Shoulder Elbow Surg. 2013 Dec;22(12):1702-9. doi: 10.1016/j.jse.2013.03.014. PubMed PMID: 23664745; PubMed Central PMCID: PMC3806888.

Joshi SK, Liu X, Samagh SP, Lovett DH, Bodine SC, Kim HT, Feeley BT. mTOR regulates fatty infiltration through SREBP-1 and PPARγ after a combined massive rotator cuff tear and suprascapular nerve injury in rats. J Orthop Res. 2013 May;31(5):724-30. doi: 10.1002/jor.22254. PubMed PMID: 23239524; PubMed Central PMCID: PMC4393845.

Samagh SP, Kramer EJ, Melkus G, Laron D, Bodendorfer BM, Natsuhara K, Kim HT, Liu X, Feeley BT. MRI quantification of fatty infiltration and muscle atrophy in a mouse model of rotator cuff tears. J Orthop Res. 2013 Mar;31(3):421-6. doi:10.1002/jor.22233. PubMed PMID: 22991068.

Piper SL, Laron D, Manzano G, Pattnaik T, Liu X, Kim HT, Feeley BT. A comparison of lidocaine, ropivacaine and dexamethasone toxicity on bovine tenocytes in culture. J Bone Joint Surg Br. 2012 Jun;94(6):856-62. doi: 10.1302/0301-620X.94B6.29063. PubMed PMID: 22628605.

Liu X, Laron D, Natsuhara K, Manzano G, Kim HT, Feeley BT. A mouse model of massive rotator cuff tears. J Bone Joint Surg Am. 2012 Apr 4;94(7):e41. doi:10.2106/JBJS.K.00620. PubMed PMID: 22488625.

Liu X, Joshi SK, Samagh SP, Dang YX, Laron D, Lovett DH, Bodine SC, Kim HT, Feeley BT. Evaluation of Akt/mTOR activity in muscle atrophy after rotator cuff tears in a rat model. J Orthop Res. 2012 Sep;30(9):1440-6. doi: 10.1002/jor.22096. PubMed PMID: 22378614.

Laron D, Samagh SP, Liu X, Kim HT, Feeley BT. Muscle degeneration in rotator cuff tears. J Shoulder Elbow Surg. 2012 Feb;21(2):164-74. doi: 10.1016/j.jse.2011.09.027. Review. PubMed PMID: 22244059.

Liu X, Manzano G, Kim HT, Feeley BT. A rat model of massive rotator cuff tears. J Orthop Res. 2011 Apr;29(4):588-95. doi: 10.1002/jor.21266. PubMed PMID:  20949443.

Clinical Studies

Several studies have been done evaluating the clinical outcomes in rotator cuff injury and repair.  We are also looking at how high resolution MRI can be used to detect changes in muscle quality with Drew Lansdown, MD and the imaging experts at UCSF. 

Naimark M, Zhang AL, Leon I, Trivellas A, Feeley BT, Ma CB. Clinical, Radiographic, and Surgical Presentation of Subscapularis Tendon Tears: A Retrospective Analysis of 139 Patients. Arthroscopy. 2016 May;32(5):747-52. doi: 10.1016/j.arthro.2015.11.019. PubMed PMID: 26786827.

Feeley BT. CORR Insights(®): What is the Best Clinical Test for Assessment of the Teres Minor in Massive Rotator Cuff Tears? Clin Orthop Relat Res. 2015 Sep;473(9):2967-8. doi: 10.1007/s11999-015-4420-9. PubMed PMID: 26100259; PubMed Central PMCID: PMC4523546.

Berliner JL, Regalado-Magdos A, Ma CB, Feeley BT. Biomechanics of reverse total shoulder arthroplasty. J Shoulder Elbow Surg. 2015 Jan;24(1):150-60. doi: 10.1016/j.jse.2014.08.003. Review. PubMed PMID: 25441574.

Zhang AL, Theologis AA, Tay B, Feeley BT. The association between cervical spine pathology and rotator cuff dysfunction. J Spinal Disord Tech. 2015 May;28(4):E206-11. doi: 10.1097/BSD.0000000000000223. PubMed PMID: 25393668.

Feeley BT, Zhang AL, Barry JJ, Shin E, Ho J, Tabaraee E, Ma CB. Decreased scapular notching with lateralization and inferior baseplate placement in reverse shoulder arthroplasty with high humeral inclination. Int J Shoulder Surg. 2014 Jul;8(3):65-71. doi: 10.4103/0973-6042.140112. PubMed PMID: 25258496; PubMed Central PMCID: PMC4168654.

Kiet TK, Feeley BT, Naimark M, Gajiu T, Hall SL, Chung TT, Ma CB. Outcomes after shoulder replacement: comparison between reverse and anatomic total shoulder arthroplasty. J Shoulder Elbow Surg. 2015 Feb;24(2):179-85. doi:10.1016/j.jse.2014.06.039. PubMed PMID: 25213827.

Iyengar JJ, Samagh SP, Schairer W, Singh G, Valone FH 3rd, Feeley BT. Current trends in rotator cuff repair: surgical technique, setting, and cost. Arthroscopy. 2014 Mar;30(3):284-8. doi: 10.1016/j.arthro.2013.11.018. PubMed PMID: 24468325.

Barry JJ, Lansdown DA, Cheung S, Feeley BT, Ma CB. The relationship between tear severity, fatty infiltration, and muscle atrophy in the supraspinatus. J Shoulder Elbow Surg. 2013 Jan;22(1):18-25. doi: 10.1016/j.jse.2011.12.014. PubMed PMID: 22541866.

Lansdown DA, Feeley BT. Evaluation and treatment of rotator cuff tears. Phys Sportsmed. 2012 May;40(2):73-86. doi: 10.3810/psm.2012.05.1967. Review. PubMed PMID: 22759608.

Cheung S, Dillon E, Tham SC, Feeley BT, Link TM, Steinbach L, Ma CB. The presence of fatty infiltration in the infraspinatus: its relation with the condition of the supraspinatus tendon. Arthroscopy. 2011 Apr;27(4):463-70. doi: 10.1016/j.arthro.2010.09.014. PubMed PMID: 21277734.

Feeley BT, Gallo RA, Craig EV. Cuff tear arthropathy: current trends in diagnosis and surgical management. J Shoulder Elbow Surg. 2009 May-Jun;18(3):484-94. doi: 10.1016/j.jse.2008.11.003. Review. PubMed PMID: 19208484.