Purpose
Cellular proliferation is accompanied by cellular apoptosis. In the healing digital
flexor tendon, molecular events concerning cellular apoptosis have not been investigated.
This study aimed to investigate the relationship between cellular apoptosis and proliferation
in early tendon healing.
Methods
The flexor digitorum profundus tendons of 50 long toes in 25 chickens were transected
and were repaired surgically. On postoperative days 3, 7, 14, 21, and 28, we subjected
tendons to in situ terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL) assay to detect
apoptotic cells, immunofluorescence staining with antibodies to proliferating cell
nuclear antigen to assess proliferation, and Bcl-2, an anti-apoptotic protein, to
assess responses suppressive to apoptosis. The positively labeled tenocytes were counted
microscopically and compared statistically. We also stained sections with hematoxylin
and eosin to observe their healing status. An additional 12 tendons (6 chickens) served
as day 0 controls.
Results
Compared with tendons at day 0, the healing tendons had notably greater cellularity
in both epitenon and endotenon areas. The total number of cells and number of TUNEL-positive
cells peaked at day 3. At days 7 to 21, the number of proliferating cell nuclear antigen–positive
cells peaked. At days 7 and 14, the cells positively stained with Bcl-2 peaked. At
days 14 to 28, the total number of cells and TUNEL-positive cells decreased significantly
compared with those at days 3 and 7, yet the numbers remained greater than those on
day 0.
Conclusions
Apoptosis in the healing tendons peaks at day 3, followed about 10 days later by the
peak proliferation period. Because Bcl-2 serves to inhibit apoptosis, a later increase
in Bcl-2–positive cells indicates that tendon apoptosis is inhibited. These findings
indicate that tenocyte apoptosis is accelerated within several days after injury,
followed by increases in cellular proliferation and activation of molecular events
to inhibit apoptosis in 2 to 4 weeks.
Key words
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References
- Growth factors and canine flexor tendon healing: initial studies in uninjured and repair models.J Hand Surg. 1995; 20A: 645-649
- Effect of basic fibroblast growth factor.Clin Orthop Relat Res. 1997; 342: 239-247
- Molecular studies in flexor tendon wound healing: the role of basic fibroblast growth factor gene expression.J Hand Surg. 1998; 23A: 1052-1058
- Inhibition of TGF-beta-induced collagen production in rabbit flexor tendons.J Hand Surg. 2004; 29A: 230-235
- Tendon healing in vitro: bFGF gene transfer to tenocytes by adeno-associated viral vectors promotes expression of collagen genes.J Hand Surg. 2005; 30A: 1255-1261
- Adeno-associated virus-2-mediated bFGF gene transfer to digital flexor tendons significantly increases healing strength.J Bone Joint Surg. 2008; 90A: 1078-1089
- Caspases: the executioners of apoptosis.Biochem J. 1997; 326: 1-16
- Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf.Nature. 2004; 430: 213-218
- BCL-2 family: regulators of cell death.Annu Rev Immunol. 1998; 16: 395-419
- Modulation of cell functions of human tendon fibroblasts by different repetitive cyclic mechanical stress patterns.Exp Toxicol Pathol. 2003; 55: 153-158
- Cyclic mechanical stretching of human patellar tendon fibroblasts: activation of JNK and modulation of apoptosis.Knee Surg Sports Traumatol Arthrosc. 2003; 11: 122-129
- High strain mechanical loading rapidly induces tendon apoptosis: an ex vivo rat tibialis anterior model.Br J Sports Med. 2005; 39: e25
- Apoptosis in rotator cuff tendinopathy.J Orthop Res. 2002; 20: 1372-1379
- Cell death and tendinopathy.Clin Sports Med. 2003; 22: 693-701
- Increased apoptosis at the late stage of tendon healing.Wound Repair Regen. 2007; 15: 702-707
- IFSSH Flexor Tendon Committee Report 2007.J Hand Surg. 2007; 32E: 346-356
- The rupture rate of acute flexor tendon repairs mobilized by the controlled active motion regimen.J Hand Surg. 1994; 19B: 607-612
- Indications, methods, postoperative motion and outcome evaluation of primary flexor tendon repairs in Zone 2.J Hand Surg. 2007; 32E: 118-129
- Effect of motion and tension on injured flexor tendons in chickens.J Hand Surg. 1996; 21A: 456-463
- Clinical outcomes associated with flexor tendon repair.Hand Clin. 2005; 21: 199-210
- Some practical notes on the anatomy of chicken toe for surgeon investigators.Plast Reconstr Surg. 1974; 54: 452-458
- Experimental studies in chickens on the initial nutrition of tendon grafts.J Hand Surg. 1979; 4A: 565-575
- Effect of flexor sheath integrity on tendon gliding: a biomechanical and histologic study.J Orthop Res. 1986; 4: 458-465
- Effects of superficialis tendon repairs on lacerated profundus tendons within or proximal to the A2 pulley: an in vivo study in chickens.J Hand Surg. 2003; 28A: 944-1001
- Digital oedema, adhesion formation and resistance to digital motion after primary flexor tendon repair.J Hand Surg. 2008; 33E: 745-752
- Effectiveness of microRNA in down regulation of TGF-β gene expression in digital flexor tendons of chickens: in vitro and in vivo study.J Hand Surg. 2009; 34E: 1777-1784
- Determination of the proliferation and apoptotic index in adrenocorticotropin-secreting pituitary tumors: comparison between micro- and macroadenomas.Am J Pathol. 2000; 156: 245-251
- Prognostic significance of apoptotic index in completely resected non–small-cell lung cancer.J Clin Oncol. 1999; 17: 2728-2736
- Effect of glycaemic control on apoptosis in diabetic wounds.J Wound Care. 2005; 14: 277-281
- Multiple roles of the proliferating cell nuclear antigen: DNA replication, repair and cell cycle control.Prog Cell Cycle Res. 1997; 3: 193-210
- The inflammatory response and hyaluronan synthases in the rabbit flexor tendon and tendon sheath following injury.J Hand Surg. 2007; 32E: 581-587
- Quantitative variation in vascular endothelial growth factor mRNA expression during early flexor tendon healing: an investigation in a canine model.J Orthop Res. 2001; 19: 869-872
- Genetic expression for type I procollagen in the early stages of flexor tendon healing.J Hand Surg. 1992; 17A: 551-558
- UVA-induced apoptosis studied by the new apo/necro-Comet-assay which distinguishes viable, apoptotic and necrotic cells.Mutagenesis. 2006; 21: 105-114
- Identifying and quantifying apoptosis: navigating technical pitfalls.Mod Pathol. 2003; 16: 389-394
Article info
Publication history
Accepted:
October 20,
2009
Received:
April 21,
2009
Footnotes
No benefits in any form have been received or will be received related directly or indirectly to the subject of this article.
Identification
Copyright
© 2010 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Molecular Events of Cellular Apoptosis and Proliferation in the Early Tendon Healing PeriodJournal of Hand SurgeryVol. 35Issue 4
- PreviewIt was with great interest that we read the article by Wu et al. about apoptosis and proliferation in the early tendon healing period.1 In an animal model, they were able to establish that apoptotic processes peak at day 3 in healing tendons. Furthermore, they found evidence of increased tenocyte proliferation and inhibition of apoptosis occurring a few days later.
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