Dr Andrew Hall

We are currently studying the physiology of in situ chondrocytes exhibiting normal or abnormal morphology, to try to determine what causes the changes in shape and hence matrix metabolism that characterise osteoarthritis.

Personal profile

• 2007 - present: Reader
• 1998 - 2007: Senior Lecturer, University of Edinburgh
• 1996 - 1998: Lecturer, University of Edinburgh (Wellcome Trust University Award 1996-2001)
• 1992 - 1996: Wellcome Trust Senior Research Fellow, University Laboratory of Physiology, Oxford
• 1986 - 1992: University Demonstrator, University Laboratory of Physiology, Oxford
• Visiting Research Associate, University of Alberta, Edmonton
• 1983 - 1986: Research Associate to Dr JC Ellory, Physiological Laboratory, Cambridge
• 1981 - 1983: Research Associate Department of Physiology and Biophysics, University of Illinois

Research Theme

• Ageing and Degeneration
• Injury and Repair

Dr Andrew Hall's research briefing

1. How can we protect chondrocytes against iatrogenic injury during surgery?

Articular cartilage normally has an extraordinary capacity to withstand and adapt to the physiological loads associated with joint activity. However its ability to cope with unphysiological trauma is limited and this can result in permanent cartilage damage and death of cartilage cells (chondrocytes), potentially leading to cartilage failure and osteoarthritis (OA).

During routine orthopaedic surgery, cartilage can be exposed to injury caused by accident or design. This injury is called ‘iatrogenic’ (‘originating from a physician’ - an ‘inadvertent adverse effect or complication resulting from a medical procedure’). For example during arthroscopy, cartilage is probed and scraped and sharp points or edges of the arthroscopic sheath can inadvertently gouge and damage cartilage. During open orthopaedic surgery, hyaline cartilage and other connective/soft tissues (e.g. meniscus, synovium) are deliberately subjected to injury as a result of trimming/debridement or cutting using standard but (normally) sharp surgical instruments including scalpel blades and curettes. Insertion of articular screws in disorders e.g. osteochondritis dissecans, exposes cartilage to both sharp and blunt trauma through drilling or impaction and this has been associated with loss of chondrocyte viability (Houston et al., 2013). Cartilage and other connective tissues may also dry out during open surgery and this can cause chondrocyte death although the mechanism is currently unknown.

Adult articular cartilage has a very limited ability to repair and the matrix that is produced is mechanically incompetent and wears away quickly. In addition, once skeletal maturity is reached, chondrocytes are not replaced, and so if they die, areas of cartilage remain which are highly susceptible to degeneration and development of OA. Everything possible should be done to protect chondrocytes during orthopaedic surgery.

We have found that raising the osmotic pressure of the irrigation fluid used during routine orthopaedic surgery can give substantial protection to chondrocytes during mechanical injury (Fig. 1). These findings might have relevance for improving current orthopaedic surgery.

Fig. 1. Protection of articular chondrocytes against scalpel injury by hyper-osmotic saline.

Panel A shows the injury created following a single scalpel cut to bovine cartilage (living cells green, dead cells dead) and

(B) reduced cell death when irrigated with raised osmolarity. (Scale bar 50µm).

(Images courtesy of Dr N. Eltawil).

2. What is the role of articular chondrocytes in osteoarthritis?

Osteoarthritis (OA) is an increasingly common, painful and debilitating syndrome of human articular cartilage. It used to be thought that it arose from cartilage ‘wear-and-tear’, but there is increasing evidence that changes to the physiology of chondrocytes plays a key role, although the details are largely unclear.

Human chondrocytes are normally ellipsoidal/spheroidal in shape, but using confocal microscopy and our state-of-the-art imaging facility (see IMPACT imaging facility) which enables the visualisation of the fine details of living cells within their native environment, we have observed chondrocytes with remarkable cytoplasmic ‘processes’ extending for significant distances from the cell body (Fig. 2; Bush & Hall 2003). These are present even in non-degenerate cartilage, and preliminary work suggests their incidence increases markedly with the degree of OA.

Changes to chondrocyte morphology alter the type and mechanical properties of the extracellular matrix which the cells produce. Are these changes to morphology an early and preventable step in the development of OA? We are currently studying the physiology of in situ chondrocytes which exhibit normal or abnormal morphology, to try to determine what causes the changes in shape and hence matrix metabolism that characterise OA. We

are also developing a three-dimensional culture system to study the factors involved in the regulation of chondrocyte morphology under more defined conditions.

IMPACT imaging facility

Fig. 2. Morphology of human chondrocytes within tibial plateau cartilage.

(A) shows the spheroidal appearance of ‘normal’ chondrocytes and (B) an example of a morphologically-abnormal chondrocyte with extensive cytoplasmic processes. Cartilage was grade 0 i.e. macroscopically normal and non-degenerate.

Other areas of Research Interest.

• Septic arthritis - in particular the effects of toxins from Staphylococcus aureus on the viability of articular chondrocytes (Smith et al., 2013)
• Chondrocyte hypertrophy in the mammalian growth plate – a role for membrane transporters? (Loqman et al., 2013).
• Morphology and matrix metabolism by chondrocytes in strong and weak gel cultures, and on artificial membranes (Karim et al., 2016; Hindle et al., 2014)
• Regulation of [Ca²⁺]_i and pH_i by in situ chondrocytes (Simpkin et al., 2007).

Team members

• Mr Rhys Clement (PhD student)
• Ms Ellie Davidson (MD student)
• Ms Kathryn McCall (PhD student)

Collaborations

• Prof. Hamish Simpson, Orthopaedics, University of Edinburgh
• Dr Anish Amin, Orthopaedics, University of Edinburgh.
• Dr Peter Bush, University of Brighton

Publications

Eltawil, N.M., Ahmed, S., Chan, L.H., Simpson, A.H.R.W. & Hall, A.C. (2016). Chondroprotection in a model of cartilage injury by raising the temperature and osmolarity of arthroscopic irrigation solutions. Cartilage - in Press

Paterson, S.I., Eltawil, N.M., Simpson, A.H.R.W., Amin, A.K. & Hall, A.C. (2016). Drying of open animal joints in vivo subsequently causes cartilage degeneration. Bone Jt. Res. 5:137-144.

Karim, A. & Hall, A.C. (2016a). Chondrocyte morphology in stiff and soft agarose gels and the influence of fetal calf serum. J. Cell Physiology 232(5):1041-1052.

Karim, A & Hall, A.C. (2016b). Hyperosmolarity normalizes serum-induced changes to chondrocyte properties in a model of cartilage injury. Europ. Cells & Mat. 31:205-220.

Lin, Y-C., Hall, A.C., Smith, I.D.M., Salter, D.M. & Simpson, A.H.R.W. (2016). Mapping chondrocyte viability, matrix glycosaminoglycan content, and water content on the surface of a bovine metatarsophalangeal joint. Cartilage 7(2):193-203.

Eltawil NM, Howie SE, Simpson AH, Amin AK, Hall AC. (2015). The use of hyperosmotic saline for chondroprotection: implications for orthopaedic surgery and cartilage repair. Osteoarthritis Cartilage. 23(3):469-77.

Paterson SI, Amin AK, Hall AC. (2015) Airflow accelerates bovine and human articular cartilage drying and chondrocyte death. Osteoarthritis Cartilage. 23(2):257-65.

Hindle P, Hall AC, Biant LC. (2014) Viability of chondrocytes seeded onto a collagen I/III membrane for matrix-induced autologous chondrocyte implantation. J Orthop Res. 32(11):1495-502.

Farhan-Alanie MM, Hall AC. (2014) Temperature changes and chondrocyte death during drilling in a bovine cartilage model and chondroprotection by modified irrigation solutions. Int Orthop. 38(11):2407-12.

Smith, I. D. M., J. P. Winstanley, K. M. Milto, C. J. Doherty, E. Czarniak, S. G. B. Amyes, A. Simpson and A. C. Hall (2013). Rapid in situ chondrocyte death induced by Staphylococcus aureus toxins in a bovine cartilage explant model of septic arthritis. Osteoarthritis and Cartilage 21(11): 1755-1765.

Loqman, M.Y., Farquharson, C., Bush, P.G. & Hall, A.C. (2013). Suppression of mammalian bone growth by membrane transport inhibitors. J. Cell Biochem. 114:658-668.

Houston, D.A., Amin, A.K., White, T.O., Smith, I.D., & Hall, A.C. (2013). Chondrocyte death after drilling and screw placement in a bovine model. Osteoarth. & Cart. 21:721-729.

Amin, A.K., Huntley, J.S., Patton, J.T., Brenkel, I.J., Simpson, A.H.W.R. & Hall, A.C. (2011). Hyperosmolarity protects chondrocytes from mechanical injury in human articular cartilage: An experimental report. J. Bone Jt. Surg. (Br). 93(2), 277-284.

Murray, D.H., Bush, P.G., Brenkel, I.J. & Hall, A.C. (2010). Abnormal human chondrocyte morphology is related to increased levels of cell-associated IL-1? and disruption to pericellular collagen type VI. J. Orthop. Res.28(11), 1507-1514.

Amin, A.K., Huntley, J.S., Simpson, A.H.R.W. & Hall, A.C. (2010). Increasing the osmolarity of joint irrigation solutions may avoid injury to cartilage: A pilot study. Clin. Orthop. Related Res. 468, 875-884

Amin, A.K., Huntley, J.S., Simpson, A.H.W. & Hall, A.C. (2009). Chondrocyte survival in articular cartilage: the influence of subchondral bone in a bovine model. J. Bone Jt. Surg. (Br).91 B:691-699.

Simpkin, V.L., Murray, D.H., Hall, A.P. & Hall, A.C. (2007). Bicarbonate-dependent pHi regulation by chondrocytes within the superficial zone of bovine articular cartilage. J. Cell. Physiol. 212(3):600-609.

Bush, P.G., Hodkinson, P.D., Hamilton, G.L., & Hall, A.C. (2005). Viability and volume of in situ bovine articular chondrocytes - changes following a single impact and effects of medium osmolarity. Osteoarth. & Cart. 13, 54-65.

Bush, P.G. & Hall, A.C. (2003). The volume and morphology of chondrocytes within non-degenerate and degenerate human articular cartilage. Osteoarth. Cart. 11(4):242-251.

Andrew Hall publication list (PDF)

Information for students:

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